title: BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis.
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.
  
  
  RESULTS
  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
  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.
authors: Division of Rheumatology, Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
authors: Xiaohui
authors: X
authors: Zhou
authors: Zanxian
authors: Z
authors: Xia
authors: Qin
authors: Q
authors: Lan
authors: Julie
authors: J
authors: Wang
authors: Wenru
authors: W
authors: Su
authors: Yuan-Ping
authors: YP
authors: Han
authors: Huimin
authors: H
authors: Fan
authors: Zhongmin
authors: Z
authors: Liu
authors: William
authors: W
authors: Stohl
authors: Song Guo
authors: SG
authors: Zheng
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D053264:B-Cell Activating Factor; D019947:Receptors, Interleukin-6