BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis

Xiaohui Zhou, Zanxian Xia, Qin Lan, Julie Wang, Wenru Su, Yuan Ping Han, Huimin Fan, Zhongmin Liu, William Stohl, Song Guo Zheng

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Background: BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE. Methodology/Principal Findings: Th17 cells were increased in BAFF-Tg B6 (B6.BTg) mice and decreased in B6.Baff -/- mice. Th17 cells in B6.Baff -/- mice bearing a BAFF Tg (B6.Baff -/-.BTg mice) were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff -/- T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4 + cell expression of CD126 (IL-6R α chain) was increased in B6.BTg mice and decreased in B6.Baff -/- mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff -/- cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff -/- mice and correlated with MOG 35-55 peptide-induced Th17 cell responses. Conclusions/Significance: Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases.

Original languageEnglish (US)
Article numbere23629
JournalPloS one
Volume6
Issue number8
DOIs
StatePublished - Aug 29 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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