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5. Normal lymphocyte homeostasis and function in MALT1 protease‐resistant HOIL‐1 knock‐in mice.

Author

Skordos, Ioannis, Driege, Yasmine, Haegman, Mira, Kreike, Marja, Staal, Jens, Demeyer, Annelies, and Beyaert, Rudi

Subjects
REGULATORY T cells, LYMPHOCYTES, HOMEOSTASIS, B cells, MICE, UBIQUITIN ligases, NF-kappa B
Abstract

The uniqueness of MALT1 protease activity in controlling several aspects of immunity in humans has made it a very attractive therapeutic target for multiple autoimmune diseases and lymphoid malignancies. Despite several encouraging preclinical studies with MALT1 inhibitors, severe reduction in regulatory T cells and immune‐mediated pathology seen in MALT1 protease‐dead (MALT1‐PD) mice and some, but not all, studies analysing the effect of prolonged pharmacological MALT1 protease inhibition, indicates the need to further unravel the mechanism of MALT1 protease function. Notably, the contribution of individual MALT1 substrates to the immune defects seen in MALT1‐PD mice is still unclear. Previous in vitro studies indicated a role for MALT1‐mediated cleavage of the E3 ubiquitin ligase HOIL‐1 in the modulation of nuclear factor‐κB (NF‐κB) signalling and inflammatory gene expression in lymphocytes. Here, we addressed the immunological consequences of inhibition of HOIL‐1 cleavage by generating and immunophenotyping MALT1 cleavage‐resistant HOIL‐1 knock‐in (KI) mice. HOIL‐1 KI mice appear healthy and have no overt phenotype. NF‐κB activation in T or B cells, as well as IL‐2 production and in vitro T‐cell proliferation, is comparable between control and HOIL‐1 KI cells. Inhibition of HOIL‐1 cleavage in mice has no effect on thymic T‐cell development and conventional T‐cell homeostasis. Likewise, B‐cell development and humoral immune responses are not affected. Together, these data exclude an important role of MALT1‐mediated HOIL‐1 cleavage in T‐ and B‐cell development and function in mice. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures

Author

Meireson, Annabel, primary, Tavernier, Simon J., additional, Van Gassen, Sofie, additional, Sundahl, Nora, additional, Demeyer, Annelies, additional, Spaas, Mathieu, additional, Kruse, Vibeke, additional, Ferdinande, Liesbeth, additional, Van Dorpe, Jo, additional, Hennart, Benjamin, additional, Allorge, Delphine, additional, Haerynck, Filomeen, additional, Decaestecker, Karel, additional, Rottey, Sylvie, additional, Saeys, Yvan, additional, Ost, Piet, additional, and Brochez, Lieve, additional

Published
2021
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11. Deletion of Mucosa‐Associated Lymphoid Tissue Lymphoma Translocation Protein 1 in Mouse T Cells Protects Against Development of Autoimmune Arthritis but Leads to Spontaneous Osteoporosis

Author

Gilis, Elisabeth, primary, Gaublomme, Djoere, additional, Staal, Jens, additional, Venken, Koen, additional, Dhaenens, Maarten, additional, Lambrecht, Stijn, additional, Coudenys, Julie, additional, Decruy, Tine, additional, Schryvers, Nadia, additional, Driege, Yasmine, additional, Dumas, Emilie, additional, Demeyer, Annelies, additional, De Muynck, Amélie, additional, Hengel, Jolanda, additional, Van Hoorebeke, Luc, additional, Deforce, Dieter, additional, Beyaert, Rudi, additional, and Elewaut, Dirk, additional

Published
2019
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15. Cleavage by MALT1 induces cytosolic release of A20

Author

Malinverni, Claire, primary, Unterreiner, Adeline, additional, Staal, Jens, additional, Demeyer, Annelies, additional, Galaup, Marion, additional, Luyten, Marcel, additional, Beyaert, Rudi, additional, and Bornancin, Frédéric, additional

Published
2010
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