The IL‐27/IL‐27R axis is altered in CD4 + and CD8 + T lymphocytes from multiple sclerosis patients - Sorbonne Université
Journal Articles Clinical and Translational Immunology Year : 2021

The IL‐27/IL‐27R axis is altered in CD4 + and CD8 + T lymphocytes from multiple sclerosis patients

Abstract

Objectives: Pro- and anti-inflammatory properties have been attributed to interleukin-27 (IL-27). Nevertheless, the impact of this cytokine on chronic inflammatory diseases such as multiple sclerosis (MS) remains ill-defined. We investigated the biology of IL-27 and its specific receptor IL-27Rα in MS patients. Methods: Levels of IL-27 and its natural antagonist (IL-27-Rα) were measured by ELISA in biological fluids. CD4+ and CD8+ T lymphocytes were isolated from untreated relapsing-remitting MS patients and healthy donors. Transcriptome-wide analysis compared T-cell subsets stimulated or not with IL-27. Expression of the IL-27Rα, key immune factors, STAT phosphorylation and cytokine production was assessed by flow cytometry. Results: We observed elevated levels of IL-27 in the serum and cerebrospinal fluid of MS patients compared with controls. Moreover, we show that specific IL-27-mediated effects on T lymphocytes are reduced in MS patients including the induction of PD-L1. IL-27-triggered STAT3 signalling pathway is enhanced in CD4+ and CD8+ T lymphocytes from MS patients. Elevated IL-27Rα levels in serum from MS patients are sufficient to impair the capacity of IL-27 to act on immune cells. We demonstrate that shedding of IL-27Rα by activated CD4+ T lymphocytes from MS patients contributes to the increased IL-27Rα peripheral levels and consequently can dampen the IL-27 responsiveness. Conclusion: Our work identifies several mechanisms that are altered in the IL-27/IL-27R axis in MS patients, especially in T lymphocytes. Our results underline the importance of characterising the biology of cytokines in human patients prior to design new therapeutics.
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Dates and versions

hal-03208150 , version 1 (26-04-2021)

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Marie-Laure Clénet, Cyril Laurent, Florent Lemaitre, Negar Farzam-Kia, Olivier Tastet, et al.. The IL‐27/IL‐27R axis is altered in CD4 + and CD8 + T lymphocytes from multiple sclerosis patients. Clinical and Translational Immunology, 2021, 10 (3), pp.e1262. ⟨10.1002/cti2.1262⟩. ⟨hal-03208150⟩
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