期刊
IMMUNOLOGY
卷 146, 期 2, 页码 251-263出版社
WILEY
DOI: 10.1111/imm.12497
关键词
autoimmunity; experimental autoimmune encephalomyelitis/multiple sclerosis; neuroimmunology; signal transduction; T cells
类别
资金
- research fellowship FISM - Fondazione Italiana Sclerosi Multipla [cod.2010/B/3, cod.2011/B/3]
- Italian Multiple Sclerosis Society FISM - Fondazione Italiana Sclerosi Multipla [cod 2013/R/2, cod.2013/R/23]
- Italian Ministry of Health (Progetto Finalizzato)
- Italian Association for Cancer Research (AIRC)
- Biotechnology and Biological Sciences Research Council [BB/E019188/1] Funding Source: researchfish
- BBSRC [BB/E019188/1] Funding Source: UKRI
The p38 mitogen-activated protein kinase cascade is required for the induction of a T helper type 17 (Th17) -mediated autoimmune response, which underlies the development and progression of several autoimmune diseases, such as experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis (MS). However, the contribution of p38 phosphorylation to human Th cell differentiation has not been clarified. Here we demonstrate that the p38 signalling pathway is implicated in the generation of Th17 lymphocytes from human CD4(+) CD27(+) CD45RA(+) naive T cells, both in healthy donors and in patients affected by the relapsing-remitting form of MS. Our data also indicate that p38 activation is essential for interleukin-17 release from central memory lymphocytes and committed Th17 cell clones. Furthermore, CD4(+) T cells isolated from individuals with relapsing-remitting MS display an altered responsiveness of the p38 cascade, resulting in increased p38 phosphorylation upon stimulation. These findings suggest that the p38 signalling pathway, by modulating the Th17 differentiation and response, is involved in the pathogenesis of MS, and open new perspectives for the use of p38 inhibitors in the treatment of Th17-mediated autoimmune diseases.
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