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BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis
Xiaohui Zhou1, Zanxian Xia, Qin Lan
1Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
Plos One
|September 8, 2011
Summary
B-cell Activating Factor (BAFF) promotes pathogenic T helper 17 (Th17) cell generation, exacerbating EAE. BAFF antagonism may treat Th17-driven autoimmune diseases.
Area of Science:
- Immunology
- Autoimmunity
- Cellular Biology
Background:
- B-cell Activating Factor (BAFF) is known to influence B cell survival and differentiation.
- Emerging evidence suggests BAFF may also impact T cell populations.
- The role of BAFF in T helper 17 (Th17) cell development and Th17-driven diseases remains to be fully elucidated.
Purpose of the Study:
- To investigate the effect of BAFF on Th17 cell generation.
- To determine the implications of BAFF-mediated Th17 cell changes in experimental autoimmune encephalomyelitis (EAE), a model for Th17 cell-driven disease.
Main Methods:
- Comparative analysis of Th17 cell populations in BAFF-transgenic (BAFF-Tg) and BAFF-deficient (Baff-/-) mice.
- In vitro co-culture experiments to assess Th17 cell differentiation.
- Flow cytometry to analyze CD4+ T cell surface marker expression (CD126/IL-6Rα).
- Assessment of STAT3 activation following cytokine stimulation.
- Clinical and pathological evaluation of EAE severity.
Main Results:
- Th17 cell numbers were significantly increased in BAFF-Tg mice and decreased in Baff-/- mice.
- Soluble BAFF, not membrane-bound BAFF, is crucial for Th17 cell generation.
- BAFF influences Th17 cell differentiation via modulation of IL-6Rα expression and STAT3 activation.
- EAE severity correlated directly with Th17 cell responses and BAFF levels.
Conclusions:
- BAFF plays a significant role in promoting pathogenic Th17 cell responses.
- These findings highlight BAFF as a potential therapeutic target for Th17 cell-driven autoimmune diseases.
- BAFF antagonism may offer a promising strategy for treating conditions like EAE.
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