8 results on '"Rauld, Celine"'
Search Results
2. Innate acting memory Th1 cells modulate heterologous diseases.
- Author
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Rakebrandt, Nikolas, Yassini, Nima, Kolz, Anna, Schorer, Michelle, Lambert, Katharina, Goljat, Eva, Brull, Anna Estrada, Rauld, Celine, Balazs, Zsolt, Krauthammer, Michael, Carballido, José M., Peters, Anneli, and Joller, Nicole
- Subjects
TH1 cells ,LEGIONELLA pneumophila ,IMMUNOLOGIC memory ,T helper cells ,DISEASE susceptibility - Abstract
Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. The Emerging Jamboree of Transformative Therapies for Autoimmune Diseases.
- Author
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Carballido, José M., Regairaz, Camille, Rauld, Celine, Raad, Layla, Picard, Damien, and Kammüller, Michael
- Subjects
AUTOIMMUNE diseases ,IMMUNOLOGICAL tolerance ,ROOT diseases ,B cells ,T cells - Abstract
Standard treatments for autoimmune and autoinflammatory disorders rely mainly on immunosuppression. These are predominantly symptomatic remedies that do not affect the root cause of the disease and are associated with multiple side effects. Immunotherapies are being developed during the last decades as more specific and safer alternatives to small molecules with broad immunosuppressive activity, but they still do not distinguish between disease-causing and protective cell targets and thus, they still have considerable risks of increasing susceptibility to infections and/or malignancy. Antigen-specific approaches inducing immune tolerance represent an emerging trend carrying the potential to be curative without inducing broad immunosuppression. These therapies are based on antigenic epitopes derived from the same proteins that are targeted by the autoreactive T and B cells, and which are administered to patients together with precise instructions to induce regulatory responses capable to restore homeostasis. They are not personalized medicines, and they do not need to be. They are precision therapies exquisitely targeting the disease-causing cells that drive pathology in defined patient populations. Immune tolerance approaches are truly transformative options for people suffering from autoimmune diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
4. Imaging Mass Cytometry and Single-Cell Genomics Reveal Differential Depletion and Repletion of B-Cell Populations Following Ofatumumab Treatment in Cynomolgus Monkeys.
- Author
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Theil, Diethilde, Smith, Paul, Huck, Catherine, Gilbart, Yoann, Kakarieka, Algirdas, Leppert, David, Rauld, Celine, Schmid, Cindy, Baumgartner, Reto, Stuber, Nathalie, Cordoba, Francisco, Dubost, Valerie, Darribat, Katy, Jivkov, Magali, Frieauff, Wilfried, Kneuer, Rainer, Stoeckli, Markus, Reinker, Stefan, Mansfield, Keith, and Carballido, José M.
- Subjects
KRA ,CYTOMETRY ,THERAPEUTICS ,LYMPHOID tissue ,B cells - Abstract
Ofatumumab is the first, fully human, anti-CD20 monoclonal antibody in Phase 3 development for multiple sclerosis (MS). The study focused on changes in lymphocyte subsets in blood and lymphoid tissues and on potential novel biomarkers as a result of anti-CD20 antibody action in Cynomolgus monkeys treated with human equivalent doses of subcutaneous (s.c.) ofatumumab on Days 0, 7, and 14. Axillary lymph nodes (LNs) and blood samples were collected at various time points until Day 90. Lymphocyte subsets were quantified by flow cytometry, while morphological and immune cell changes were assessed by imaging mass cytometry (IMC), immunohistochemistry (IHC), in situ hybridization (ISH), and transcriptome analyses using single-cell methodology. Ofatumumab treatment resulted in a potent and rapid reduction of B cells along with a simultaneous drop in CD20
+ T cell counts. At Day 21, IHC revealed B-cell depletion in the perifollicular and interfollicular area of axillary LNs, while only the core of the germinal center was depleted of CD20+ CD21+ cells. By Day 62, the perifollicular and interfollicular areas were abundantly infiltrated by CD21+ B cells and this distribution returned to the baseline cytoarchitecture by Day 90. By IMC CD20+ CD3+ CD8+ cells could be identified at the margin of the follicles, with a similar pattern of distribution at Day 21 and 90. Single-cell transcriptomics analysis showed that ofatumumab induced reversible changes in t-distributed stochastic neighbor embedding (t-SNE) defined B-cell subsets that may serve as biomarkers for drug action. In summary, low dose s.c. ofatumumab potently depletes both B cells and CD20+ T cells but apparently spares marginal zone (MZ) B cells in the spleen and LN. These findings add to our molecular and tissue-architectural understanding of ofatumumab treatment effects on B-cell subsets. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
5. Fingerprints of CD8+ T cells on human pre-plasma and memory B cells.
- Author
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Strittmatter-Keller, Ulrike, Walter, Caroline, Rauld, Celine, Egli, Nicole, Regairaz, Camille, Rabe, Sabine, Zenke, Gerhard, Carballido, José, and Schweighoffer, Tamás
- Subjects
CD8 antigen ,DNA fingerprinting ,T cells ,PLASMA cells ,CELL differentiation ,GENE expression profiling ,TONSILS - Abstract
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
6. G-Protein-Coupled BileAcid Receptor 1 (GPBAR1,TGR5) Agonists Reduce the Production of Proinflammatory Cytokinesand Stabilize the Alternative Macrophage Phenotype.
- Author
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Högenauer, Klemens, Arista, Luca, Schmiedeberg, Niko, Werner, Gudrun, Jaksche, Herbert, Bouhelal, Rochdi, Nguyen, Deborah G., Bhat, B. Ganesh, Raad, Layla, Rauld, Celine, and Carballido, JoséM.
- Published
- 2014
- Full Text
- View/download PDF
7. Fingerprints of CD8+ T cells on human pre-plasma and memory B cells.
- Author
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Strittmatter-Keller U, Walter C, Rauld C, Egli N, Regairaz C, Rabe S, Zenke G, Carballido J, and Schweighoffer T
- Subjects
- Antigens, CD genetics, Antigens, CD metabolism, B-Lymphocyte Subsets metabolism, CD8 Antigens genetics, CD8 Antigens immunology, CD8-Positive T-Lymphocytes metabolism, Cell Differentiation immunology, Cell Separation, Cells, Cultured, Flow Cytometry, Gene Expression Profiling, Healthy Volunteers, Humans, Primary Cell Culture, RNA, Messenger analysis, Single-Cell Analysis, Tumor Necrosis Factor Receptor Superfamily, Member 7 genetics, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, B-Lymphocyte Subsets immunology, CD8 Antigens metabolism, CD8-Positive T-Lymphocytes microbiology, Cell Communication immunology, Immunologic Memory
- Abstract
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire., Competing Interests: The authors are employees of Novartis and declare no other competing interest. The commercial affiliation does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2018
- Full Text
- View/download PDF
8. G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) agonists reduce the production of proinflammatory cytokines and stabilize the alternative macrophage phenotype.
- Author
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Högenauer K, Arista L, Schmiedeberg N, Werner G, Jaksche H, Bouhelal R, Nguyen DG, Bhat BG, Raad L, Rauld C, and Carballido JM
- Subjects
- Animals, Anti-Inflammatory Agents chemistry, Calcium metabolism, Cyclic AMP metabolism, Enzyme-Linked Immunosorbent Assay, Humans, Indoles chemistry, Inflammation drug therapy, Inflammation immunology, Jurkat Cells, Lipopolysaccharides pharmacology, Macrophages drug effects, Macrophages immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes drug effects, Monocytes immunology, Niacinamide chemistry, Niacinamide pharmacology, Receptors, G-Protein-Coupled physiology, Anti-Inflammatory Agents pharmacology, Indoles pharmacology, Inflammation metabolism, Interleukin-10 metabolism, Interleukin-12 metabolism, Macrophages metabolism, Monocytes metabolism, Niacinamide analogs & derivatives, Receptors, G-Protein-Coupled agonists, Tumor Necrosis Factor-alpha metabolism
- Abstract
GPBAR1 (also known as TGR5) is a G-protein-coupled receptor (GPCR) that triggers intracellular signals upon ligation by various bile acids. The receptor has been studied mainly for its function in energy expenditure and glucose homeostasis, and there is little information on the role of GPBAR1 in the context of inflammation. After a high-throughput screening campaign, we identified isonicotinamides exemplified by compound 3 as nonsteroidal GPBAR1 agonists. We optimized this series to potent derivatives that are active on both human and murine GPBAR1. These agonists inhibited the secretion of the proinflammatory cytokines TNF-α and IL-12 but not the antiinflammatory IL-10 in primary human monocytes. These effects translate in vivo, as compound 15 inhibits LPS induced TNF-α and IL-12 release in mice. The response was GPBAR1 dependent, as demonstrated using knockout mice. Furthermore, agonism of GPBAR1 stabilized the phenotype of the alternative, noninflammatory, M2-like type cells during differentiation of monocytes into macrophages. Overall, our results illustrate an important regulatory role for GPBAR1 agonists as controllers of inflammation.
- Published
- 2014
- Full Text
- View/download PDF
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