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1. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., Stellato, C., Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., and Stellato, C.

Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for

Published
2024

2. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

CTI Research, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Jesenak, M, Levi-Schaffer, F, Nocentini, G, O'Mahony, L, Palomares, O, Redegeld, F, Sokolowska, M, Van Esch, B C A M, Stellato, C, CTI Research, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Jesenak, M, Levi-Schaffer, F, Nocentini, G, O'Mahony, L, Palomares, O, Redegeld, F, Sokolowska, M, Van Esch, B C A M, and Stellato, C

Published
2024

3. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Adcock, I M; https://orcid.org/0000-0003-2101-8843, Benito‐Villalvilla, C; https://orcid.org/0000-0002-5544-0199, Bianchini, R; https://orcid.org/0000-0003-0351-6937, Bjermer, L; https://orcid.org/0000-0002-3441-8099, Caramori, G; https://orcid.org/0000-0002-9807-327X, Cari, L; https://orcid.org/0000-0003-0698-3872, Chung, K F; https://orcid.org/0000-0001-7101-1426, Diamant, Z; https://orcid.org/0000-0003-0133-0100, Eguiluz‐Gracia, I; https://orcid.org/0000-0002-3774-931X, Knol, E F; https://orcid.org/0000-0001-7368-9820, Jesenak, M; https://orcid.org/0000-0001-7976-2523, Levi‐Schaffer, F; https://orcid.org/0000-0003-0620-2810, Nocentini, G; https://orcid.org/0000-0002-5209-0488, O'Mahony, L; https://orcid.org/0000-0003-4705-3583, Palomares, O; https://orcid.org/0000-0003-4516-0369, Redegeld, F; https://orcid.org/0000-0001-8830-7960, Sokolowska, M; https://orcid.org/0000-0001-9710-6685, Van Esch, B C A M; https://orcid.org/0000-0001-9961-750X, Stellato, C; https://orcid.org/0000-0002-1294-8355, Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Adcock, I M; https://orcid.org/0000-0003-2101-8843, Benito‐Villalvilla, C; https://orcid.org/0000-0002-5544-0199, Bianchini, R; https://orcid.org/0000-0003-0351-6937, Bjermer, L; https://orcid.org/0000-0002-3441-8099, Caramori, G; https://orcid.org/0000-0002-9807-327X, Cari, L; https://orcid.org/0000-0003-0698-3872, Chung, K F; https://orcid.org/0000-0001-7101-1426, Diamant, Z; https://orcid.org/0000-0003-0133-0100, Eguiluz‐Gracia, I; https://orcid.org/0000-0002-3774-931X, Knol, E F; https://orcid.org/0000-0001-7368-9820, Jesenak, M; https://orcid.org/0000-0001-7976-2523, Levi‐Schaffer, F; https://orcid.org/0000-0003-0620-2810, Nocentini, G; https://orcid.org/0000-0002-5209-0488, O'Mahony, L; https://orcid.org/0000-0003-4705-3583, Palomares, O; https://orcid.org/0000-0003-4516-0369, Redegeld, F; https://orcid.org/0000-0001-8830-7960, Sokolowska, M; https://orcid.org/0000-0001-9710-6685, Van Esch, B C A M; https://orcid.org/0000-0001-9961-750X, and Stellato, C; https://orcid.org/0000-0002-1294-8355

Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for st

Published
2024

4. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Afd Pharmacology, Pharmacology, Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., Stellato, C., Afd Pharmacology, Pharmacology, Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., and Stellato, C.

Published
2024

5. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.

Author

Roth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz‐Gracia, I., Knol, E. F., Jesenak, M., Levi‐Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C. A. M., and Stellato, C.

Subjects
LUNG diseases, CELLULAR aging, AGING, TASK forces, CHRONIC obstructive pulmonary disease
Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Plant-based enveloped Ara h 2 bioparticles display exceptional hypo-allergenicity

Author

Castenmiller, C., Stigler, M., Kirpas, M. E., Versteeg, S., Akkerdaas, J. H., Pena-Castellanos, G., Blokhuis, B. R., Dreskin, S. C., Auger, L., Desgagnés, R., Martel, C., Mirande, L., Morel, B., Roberge, J., Stordeur, V., Tropper, G., Vézina, L. P., Gomord, V., de Jong, E. C., Redegeld, F., Shreffler, W. G., Aglas, L., van Ree, R., Afd Pharmacology, and Pharmacology

Subjects
food allergy, hypoallergenicity, plant-based particle, Immunology, allergen immunotherapy, peanut allergy, Immunology and Allergy, bioparticle
Published
2023

7. Plant-based enveloped Ara h 2 bioparticles display exceptional hypo-allergenicity

Author

Afd Pharmacology, Pharmacology, Castenmiller, C., Stigler, M., Kirpas, M. E., Versteeg, S., Akkerdaas, J. H., Pena-Castellanos, G., Blokhuis, B. R., Dreskin, S. C., Auger, L., Desgagnés, R., Martel, C., Mirande, L., Morel, B., Roberge, J., Stordeur, V., Tropper, G., Vézina, L. P., Gomord, V., de Jong, E. C., Redegeld, F., Shreffler, W. G., Aglas, L., van Ree, R., Afd Pharmacology, Pharmacology, Castenmiller, C., Stigler, M., Kirpas, M. E., Versteeg, S., Akkerdaas, J. H., Pena-Castellanos, G., Blokhuis, B. R., Dreskin, S. C., Auger, L., Desgagnés, R., Martel, C., Mirande, L., Morel, B., Roberge, J., Stordeur, V., Tropper, G., Vézina, L. P., Gomord, V., de Jong, E. C., Redegeld, F., Shreffler, W. G., Aglas, L., and van Ree, R.

Published
2023

8. Plant‐based enveloped Ara h 2 bioparticles display exceptional hypo‐allergenicity

Author

Castenmiller, C., primary, Stigler, M., additional, Kirpas, M. E., additional, Versteeg, S., additional, Akkerdaas, J. H., additional, Pena‐Castellanos, G., additional, Blokhuis, B. R., additional, Dreskin, S. C., additional, Auger, L., additional, Desgagnés, R., additional, Martel, C., additional, Mirande, L., additional, Morel, B., additional, Roberge, J., additional, Stordeur, V., additional, Tropper, G., additional, Vézina, L. P., additional, Gomord, V., additional, de Jong, E. C., additional, Redegeld, F., additional, Shreffler, W. G., additional, Aglas, L., additional, and van Ree, R., additional

Published
2023
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9. AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

Author

Jensen‐Jarolim, E., Bax, H. J., Bianchini, R., Crescioli, S., Daniels‐Wells, T. R., Dombrowicz, D., Fiebiger, E., Gould, H. J., Irshad, S., Janda, J., Josephs, D. H., Levi‐Schaffer, F., O′Mahony, L., Pellizzari, G., Penichet, M. L., Redegeld, F., Roth‐Walter, F., Singer, J., Untersmayr, E., Vangelista, L., and Karagiannis, S. N.

Published
2018
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10. AllergoOncology: Danger signals in Allergology and Oncology. A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper

Author

Bergmann, C, Poli, A, Agache, I, Bianchini, R, Bax, H J, Castells, M, Crescioli, S, Dombrowicz, D, Ferastraoaru, D, Fiebiger, E, Gould, H J, Hartmann, K, Izquierdo, E, Jordakieva, G, Josephs, D H, Jutel, M, Levi-Schaffer, F, de Las Vecillas, L, Lotze, M T, Osborn, G, Pascal, M, Redegeld, F, Rosenstreich, D, Roth-Walter, F, Schmidt-Weber, C B, Shamji, M, Steveling, E H, Turner, M C, Untersmayr, E, Jensen-Jarolim, E, Karagiannis, S N, Bergmann, C, Poli, A, Agache, I, Bianchini, R, Bax, H J, Castells, M, Crescioli, S, Dombrowicz, D, Ferastraoaru, D, Fiebiger, E, Gould, H J, Hartmann, K, Izquierdo, E, Jordakieva, G, Josephs, D H, Jutel, M, Levi-Schaffer, F, de Las Vecillas, L, Lotze, M T, Osborn, G, Pascal, M, Redegeld, F, Rosenstreich, D, Roth-Walter, F, Schmidt-Weber, C B, Shamji, M, Steveling, E H, Turner, M C, Untersmayr, E, Jensen-Jarolim, E, and Karagiannis, S N

Abstract

The immune system interacts with many nominal ‘danger’ signals, endogenous danger-associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)-associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti-cancer immune and targeted therapies. Cross-disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes.

Published
2022

11. AllergoOncology: Danger signals in Allergology and Oncology. A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper

Author

Afd Pharmacology, Pharmacology, Bergmann, C, Poli, A, Agache, I, Bianchini, R, Bax, H J, Castells, M, Crescioli, S, Dombrowicz, D, Ferastraoaru, D, Fiebiger, E, Gould, H J, Hartmann, K, Izquierdo, E, Jordakieva, G, Josephs, D H, Jutel, M, Levi-Schaffer, F, de Las Vecillas, L, Lotze, M T, Osborn, G, Pascal, M, Redegeld, F, Rosenstreich, D, Roth-Walter, F, Schmidt-Weber, C B, Shamji, M, Steveling, E H, Turner, M C, Untersmayr, E, Jensen-Jarolim, E, Karagiannis, S N, Afd Pharmacology, Pharmacology, Bergmann, C, Poli, A, Agache, I, Bianchini, R, Bax, H J, Castells, M, Crescioli, S, Dombrowicz, D, Ferastraoaru, D, Fiebiger, E, Gould, H J, Hartmann, K, Izquierdo, E, Jordakieva, G, Josephs, D H, Jutel, M, Levi-Schaffer, F, de Las Vecillas, L, Lotze, M T, Osborn, G, Pascal, M, Redegeld, F, Rosenstreich, D, Roth-Walter, F, Schmidt-Weber, C B, Shamji, M, Steveling, E H, Turner, M C, Untersmayr, E, Jensen-Jarolim, E, and Karagiannis, S N

Published
2022

12. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Abstract

Therapeutic advances using targeted biologicals and small molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell-based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in non-oncological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in non-oncological settings such as cardiovascular disease, obesity and chronic inflammatory disorders. After describing the general features of T cell-based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell-based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.

Published
2021

13. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Published
2021

14. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Published
2021

27. AllergoOncology: microbiota in allergy and cancer - an EAACI position paper

Author

Untersmayr, E, Bax, H J, Bergmann, C, Bianchini, R, Cozen, W, Gould, H J, Hartmann, K, Josephs, D H, Levi-Schaffer, F, Penichet, M L, O'Mahony, L, Poli, A, Redegeld, F A, Roth-Walter, F, Turner, M C, Vangelista, L, Karagiannis, S N, Jensen-Jarolim, E, University of Zurich, and Karagiannis, S N

Subjects
2403 Immunology, 10183 Swiss Institute of Allergy and Asthma Research, Immunology, 2723 Immunology and Allergy, Immunology and Allergy, 610 Medicine & health
Published
2019

28. Comparing biologicals and small molecule drug therapies for chronic respiratory diseases

Author

Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E, Kolios, A, Levi-Schaffer, F, Nocentini, G, Palomares, O, Puzzovio, P G, Redegeld, F, Van Esch, B, Stellato, C, Afd Pharmacology, and Pharmacology

Abstract

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody-based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)-based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals' therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically-based formulation, offering both convenience and lower costs. Aim of this review is to compare and contrast the distinct pharmacological properties and clinical applications of SMDs- and antibody-based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for chronic inflammatory respiratory diseases. This article is protected by copyright. All rights reserved.

Published
2019

31. Butyrate inhibits human mast cell activation via epigenetic regulation of Fc?RI-mediated signaling

Author

Folkerts, Jelle, Redegeld, F, Folkerts, G, Blokhuis, B, Van Den Berg, MP, De Jong - de Bruijn, Marjolein, van Ijcken, Wilfred, Junt, T, Tam, SY, Galli, SJ, Hendriks, Rudi, Stadhouders, Ralph, Maurer, M, Folkerts, Jelle, Redegeld, F, Folkerts, G, Blokhuis, B, Van Den Berg, MP, De Jong - de Bruijn, Marjolein, van Ijcken, Wilfred, Junt, T, Tam, SY, Galli, SJ, Hendriks, Rudi, Stadhouders, Ralph, and Maurer, M

Published
2020

34. Comparing biologicals and small molecule drug therapies for chronic respiratory diseases

Author

Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E, Kolios, A, Levi-Schaffer, F, Nocentini, G, Palomares, O, Puzzovio, P G, Redegeld, F, Van Esch, B, Stellato, C, Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E, Kolios, A, Levi-Schaffer, F, Nocentini, G, Palomares, O, Puzzovio, P G, Redegeld, F, Van Esch, B, and Stellato, C

Published
2019

35. Comparing biologicals and small molecule drug therapies for chronic respiratory diseases

Author

Roth-Walter, F, Adcock, IM, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, KF, Diamant, Z, Eguiluz-Gracia, I, Knol, E, Kolios, A, Levi-Schaffer, F, Nocentini, G, Palomares, O, Puzzovio, PG, Redegeld, F, Van Esch, B, Stellato, C, Afd Pharmacology, Pharmacology, Wellcome Trust, and Commission of the European Communities

Subjects
CLUSTER-ANALYSIS, Science & Technology, Allergy, PROSTAGLANDIN D-2, Immunology, INNATE LYMPHOID-CELLS, INHIBITOR, CRTH2 ANTAGONIST, asthma, OBSTRUCTIVE PULMONARY-DISEASE, chronic obstructive pulmonary disease, DOUBLE-BLIND, ANTIBODY, COPD, antibodies, biologicals, small molecule drugs, 1107 Immunology, Life Sciences & Biomedicine
Abstract

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody-based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)-based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals' therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically-based formulation, offering both convenience and lower costs. Aim of this review is to compare and contrast the distinct pharmacological properties and clinical applications of SMDs- and antibody-based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for chronic inflammatory respiratory diseases. This article is protected by copyright. All rights reserved.

Published
2018

36. Immunoglobulin Free Light Chains in the Pathogenesis of Lung Disorders

Author

Mortaz, E., Adcock, I. M., Jamaati, H., adnan khosravi, Movassaghi, M., Garssen, J., Mogadam, M. A., Redegeld, F. A., Wellcome Trust, Afd Pharmacology, and Pharmacology

Subjects
Lung Diseases, Idiopathic pulmonary fibrosis (IPF), Chronic obstructive lungs disease (COPD), lcsh:R, Immunology, lcsh:Medicine, Free light chain, Asthma, hemic and lymphatic diseases, Humans, Immunoglobulin Light Chains, Lung cancer, Hypersensitivity pneumonitis (HP)
Abstract

Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities.

Published
2017

37. AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

Author

Jensen-Jarolim, E, Bax, H J, Bianchini, R, Crescioli, S, Daniels-Wells, T R, Dombrowicz, D, Fiebiger, Edda, Gould, H J, Irshad, S, Janda, Jozef, Josephs, D H, Levi-Schaffer, F, O Mahony, L, Pellizzari, G, Penichet, M L, Redegeld, F, Roth-Walter, F, Singer, J, Untersmayr, Eva, Vangelista, L, Karagiannis, S N, Jensen-Jarolim, E, Bax, H J, Bianchini, R, Crescioli, S, Daniels-Wells, T R, Dombrowicz, D, Fiebiger, Edda, Gould, H J, Irshad, S, Janda, Jozef, Josephs, D H, Levi-Schaffer, F, O Mahony, L, Pellizzari, G, Penichet, M L, Redegeld, F, Roth-Walter, F, Singer, J, Untersmayr, Eva, Vangelista, L, and Karagiannis, S N

Abstract

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.

Published
2018

38. AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

Author

Afd Pharmacology, Pharmacology, Jensen-Jarolim, E, Bax, H J, Bianchini, R, Crescioli, S, Daniels-Wells, T R, Dombrowicz, D, Fiebiger, Edda, Gould, H J, Irshad, S, Janda, Jozef, Josephs, D H, Levi-Schaffer, F, O Mahony, L, Pellizzari, G, Penichet, M L, Redegeld, F, Roth-Walter, F, Singer, J, Untersmayr, Eva, Vangelista, L, Karagiannis, S N, Afd Pharmacology, Pharmacology, Jensen-Jarolim, E, Bax, H J, Bianchini, R, Crescioli, S, Daniels-Wells, T R, Dombrowicz, D, Fiebiger, Edda, Gould, H J, Irshad, S, Janda, Jozef, Josephs, D H, Levi-Schaffer, F, O Mahony, L, Pellizzari, G, Penichet, M L, Redegeld, F, Roth-Walter, F, Singer, J, Untersmayr, Eva, Vangelista, L, and Karagiannis, S N

Published
2018

39. AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

Author

Jensen-Jarolim, E., primary, Bax, H. J., additional, Bianchini, R., additional, Crescioli, S., additional, Daniels-Wells, T. R., additional, Dombrowicz, D., additional, Fiebiger, E., additional, Gould, H. J., additional, Irshad, S., additional, Janda, J., additional, Josephs, D. H., additional, Levi-Schaffer, F., additional, O′Mahony, L., additional, Pellizzari, G., additional, Penichet, M. L., additional, Redegeld, F., additional, Roth-Walter, F., additional, Singer, J., additional, Untersmayr, E., additional, Vangelista, L., additional, and Karagiannis, S. N., additional

Published
2017
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40. Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells

Author

Abdi, J, Garssen, J, Faber, J, Redegeld, F A, Pharmacology, Sub General Pharmacology, Sub Immunopharmacology, Pharmacology, Sub General Pharmacology, and Sub Immunopharmacology

Subjects
Docosahexaenoic Acids, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Antineoplastic Agents, Apoptosis, Mitochondrion, Biology, Pharmacology, medicine.disease_cause, Biochemistry, Peripheral blood mononuclear cell, Bortezomib, Multiple myeloma, Cell Line, Tumor, Taverne, medicine, Humans, Molecular Biology, Membrane Potential, Mitochondrial, chemistry.chemical_classification, Arachidonic Acid, Nutrition and Dietetics, Dose-Response Relationship, Drug, Caspase 3, NF-kappa B, EPA, Boronic Acids, Eicosapentaenoic acid, Mitochondria, DHA, Eicosapentaenoic Acid, Gene Expression Regulation, chemistry, Docosahexaenoic acid, Oxidative stress, Pyrazines, Leukocytes, Mononuclear, lipids (amino acids, peptides, and proteins), Polyunsaturated fatty acid, medicine.drug, NFκB
Abstract

The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM.

Published
2015

41. AllergoOncology - the impact of allergy in oncology: EAACI position paper

Author

Jensen-Jarolim, E., primary, Bax, H. J., additional, Bianchini, R., additional, Capron, M., additional, Corrigan, C., additional, Castells, M., additional, Dombrowicz, D., additional, Daniels-Wells, T. R., additional, Fazekas, J., additional, Fiebiger, E., additional, Gatault, S., additional, Gould, H. J., additional, Janda, J., additional, Josephs, D. H., additional, Karagiannis, P., additional, Levi-Schaffer, F., additional, Meshcheryakova, A., additional, Mechtcheriakova, D., additional, Mekori, Y., additional, Mungenast, F., additional, Nigro, E. A., additional, Penichet, M. L., additional, Redegeld, F., additional, Saul, L., additional, Singer, J., additional, Spicer, J. F., additional, Siccardi, A. G., additional, Spillner, E., additional, Turner, M. C., additional, Untersmayr, E., additional, Vangelista, L., additional, and Karagiannis, S. N., additional

Published
2017
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42. Abstracts of papers

Author

Vercammen-Grandjean, A., Renoux, G., Vermeulen, N. P. E., van Bree, L., de Vries, J., Commandeur, J., Lamberts, B. B., Redegeld, F. A. M., van Schooten, F. -J., Scholte, B. J., de Vries, J., Groot, G. S. P., Laduron, Pierre M., and Blankenstein, M. A.

Published
1983
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44. Abstracts of papers pharmacological meeting

Author

Blauw, G. J., van Brummelen, P., Vermeij, P., van Zvieten, P. A., Boddeke, H. W. C. M., Doods, H. N., van Zwieten, P. A., Bom, A. H., Duncker, D. J., Verdouw, P. D., Saxena, P. R., Daemen, M. J. A. P., Vervoort-Peters, H. T. M., Thijssen, H. H. W., Davidesko, D., Batink, H. D., Bangik, H. D., van Charldrop, K. J., de Boer, S. F., Slangen, J. L., van der Gugten, J., De Loos, W. S., Bohus, B., De Jong, W., De Wied, D., de Zwart, M. A. H., van der Goot, H., Timmerman, H., Garritsen, A., IJzerman, A. P., Soudijn, W., Heynis, J. B., Boddeke, H. W. G. M., Janssen, B. J. A., van Essen, H., Boudier, H. A. J. Struyker, Smits, J. F. M., Jap, T. J. W., Ketelaars, C. E. J., Bruinvels, J., Krielaart, M. J., Veenstra, D. M. J., Stolze, G. J. T. H., le Noble, L. M. L., Slaaf, D. W., Tangelder, G. J., Neijt, H. C., te Duits, I. J., Plomp, J. J., Vijverberg, H. P. M., Raaijmakers, J. A. M., van den Eijnde, R. J. E., Radhakishun, F. S., Stoof, J. C., Mulder, A. H., Versteeg, D. H. G., van Ree, J. M., Redegeld, F. A. M., Noordhoek, J., Reul, J. M. H. M., Tonnaer, J. A. D. M., de Kloet, E. R., Riezebos, J., de Jonge, A., Sweep, C. G. J., Wiegant, V. M., van Amsterdam, F. Th. M., Haas, M., Zaagsma, J., van Amsterdam, R. G. M., Brouwer, F., van Charldorp, K. J., van de Straat, R., de Vries, J., Vermeulden, N. P. E., van Giersbergen, P. L. M., van Harten, J, Zeegers, RRECM, van Brumnelen, P, Breimer, DD, van Heiningen, P. N. M., van Hoogdalem, E. J., de Boer, A. G., Breimer, D. D., Wijngaarden, J. van, and Wesseling, H.

Published
1986
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45. Abstracts of papers

Author

Rollema, H., Grol, C. J., Feenstra, M. G. P., van Oene, Joop C., Houwing, Hendrik A., Horn, Alan S., Ijzerman, A. P., Bultsma, T., Timmerman, H., Zaagsma, J., van der Graaff, M., Vermeulen, N. P. E., Joeres, R. P., Breimer, D. D., Tsantili-Kakoulidou, A., van der Valk, F., Rekker, R. F., Bijloo, G. J., Zoetemelk, C. E. M., van Hoven, W., van Meeteren-Wālchli, B., van der Gen, A., Mohn, G. R., Buijs, W., Breimer, D. D., Onkenhout, W., de Jong, H. J., Rog, A. A., van Ginneken, C. A. M., Lentjes, E. G. W. M., Bast, A., Savenije-Chapel, E. M., Noordhoek, J., Beld A. J., Rodrigues de Miranda J. F., van Ginneken C. A. M., van der Giesen, W. F., Dröge, J. H. M., Wilting, J., Janssen, L. H. M., van Amsterdam J. G. C., van Buuren, K. J. H., Wijnne, H. J. A., Nolet, M. R. A., Kremer, J. M. H., Bakker, G., van der Heijden, P. J. C. M., van der Schaar, M. W. G., Bank, C. M. C., Eriks, J. Ch., Gaisser, H. -D., van der Goot, H., Sterk, G. J., Zaagsma, J., Lock, F. M., de Vries, J., Mullink, H., van Bree, L., Redegeld, F. A. M., Grolleman, C. W. J., de Visser, A. C., Wolke, J. G. C., Buchan, P., and Burns, J. W.

Published
1982
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46. Abstracts of Dutch doctoral theses

Author

Navis, G. J., Sterk, G. J., van Nispen, J. W., Hichens, M., Sauter, A., Lingeman, H., van den Beld, C. M. B., Tjaden, U. R., van der Greef, J., Desiderio, D. M., Cubbins, D. C., McMartin, C., Webb, R. L., Wennogle, L. P., Wysowskyi, H. E., Zimmerman, M. B., Lee, V. H. L., Sandow, J., Seidel, H., Schmiedel, R., Keller, Bradley T., Smith, Kevin R., Borchardt, Ronald T., Banks, W. A., Kastin, A. J., de Wied, D., DeLuca, P. P., Robinson, J. R., Lundin, S., Vilhardt, H., Saffran, M., Kumar, G. S., Neckers, D. G., Williams, F., Field, J. B., Jones, R. H., Panepinto, L., Harris, A. S., Moses, Alan C., Muranishi, S., Boddé, H. E., Ponec, M., Verhoef, J., Liversidge, Gary G., Boer, G. J., Kruisbrink, J., de Nijs, H., Bouwman, T. R. M., Eenink, M. J. D., Patel, Harish M., Bundgaard, H., Larsen, J. D., Nielsen, M. N., Buur, A., Tjadeh, U. R., Lemaire, M., Andres, H., Marbach, P., Widlund, L., Guilbaud, O., Wilton, P., van Bree, J. B. M. M., Audus, K. L., Deinum, Johanna, Norén, Karin, Sohtell, Morgan, Weström, B. R., Folkesson, H. G., Karlsson, B. W., Damge, C., Michel, C., Aprahamian, M., Couvreur, P., Puisieux, F., Touitou, E., Alhaique, F., Fisher, P., Memoli, A., Riccieri, F. M., Santucci, E., Hermens, W. A. J. J., Romei jn, S. G., Merkus, F. W. H. H., Schneider, C., Smith, T. W., Bremecker, K. -D., Hungerer, K. -D., Tabata, Y., Ikada, Y., Uno, K., Muramatsu, S., Bruning, J. W., Claas, F. H. J., Kardol, M. J., van Ree, J. M., Rust, C. J. J., Verduyn, W., Wiegant, V. M., Wolterink, G., van Hoogdalem, E. J., Heijligers-Feijen, C. D., de Boer, A. G., Breimer, D. D., Lambalk, C. B., van Kessel, H., de Koning, J., van Dieten, J. A. M. J., van Rees, G. P., Schoemaker, J., Devissaguet J. -Ph., Orieu K., Dray F., Ezan E., Devissaguet J. Ph., Drieu K., Dray P., Ezah E., Barnfield, D. J., Barker, Y. K., Knott, S., Miles, G. S., Warrander, A., Adam, H. K., Barker, Y., Hutchinson, F. G., Milsted, R. A. V., Moore, R. H., Swaisland, A. J., Barke, Y., Porter, E. T., Holmes, B., Barnard, M., Beijnen, J. H., Lubbers, S. C. H., van der Houwen, O. A. G. J., Lobbezoo, M. W., Underberg, W. J. M., Cachet, Th., Roets, E., Hoogmartens, J., Vanderhaeghe, H., de Bree, H., van der Stel, D. J. K., Brockhoff, O. A. M., van Berkel, M. P., Sierat, K., de Groot, G., Tepas, B. C. A., de Noord, O. E., Hempenius, J., Coenegracht, P. M. J., Jonkman, J. H. G., Doornbos, D. A., De Schutter, J. A., De Moerloose, P., Delbressine, L. P. C., Kaspersen, F. M., Blokland, A., Duchateau, A. L. L., Verstappen, T. A., Hendricks, P. J. H., Elferink, F, Leeuwenkamp, O R, Pinedo, H M, vd Vijgh, W J F, Ensing, K., Bloemhof, D. A., In 't Hout, W. G., de Zeeuw, R. A., Feitsma, Karla G., Drenth, Ben F. H., de Zeeuw, Rokus A., Gerding, T. K., Drenth, B. F. H., Horn, A. S., Groen, C. P., Tipker, J., van den Bergh-Swart, J. K., Spruit, F. J., van den Berg, J. H. M., Bramel, E. H. Groot, Bekers, O., Otagiri, M., Janssen, P. S. L., Nispen, J. W. v., Melgers, P. A. T. A., Zeeland, M. J. M. v., Hamelinck, R. L. A. E., Goverde, B. C., Aalst, G. W. M. v., Kootstra, P. R., van den Broek, H. H., Hogendoorn, E. A., Goewie, C. E., Kwakman, P. J. M., Brinkman, U. A. Th., Frei, R. W., de Jong, G. J., Lammers, N. G. F. M., Lammers, N., Ruijten, H. M., de Jong, J., Maessen, P. A., Mross, K. B., Plnedo, H. M., van der Vljgh, W. J. F., Khan, Naeem Hasan, Hoogmartens, J., Rose, S. V., van Bueren, L. G. D. Lammerts, van Amsterdam, P. H., van Beek, H., Baars, A. J., van Ginkel, L. A., Steinbuch, H. M., van Rossum, H. J., van Blitterswijk, H., Zoontjes, P. W., Heeft, E. v. d., de Jong, A. J. P. M., Stephany, R. W., van Gijn, R., de Clippeleir, J. J. M., Verweij, S. L., Paalman, A. C. A., van Opstal, M. A. J., Krabbenborg, P., Holthuis, J. J. M., van Bennekom, W. P., Bult, A., Redegeld, F. A. M., Houdkamp, E., van de Water, C., Haagsma, N., van der Stel, D. J. K., Vendrig, D. E. M. M., Mekking, A., and Teeuwsen, J.

Published
1988
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