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Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells

Young Uk Kim ; Hoyong Lim ; Ha Eun Jung ; Rick A Wetsel ; Yeonseok Chung

PLoS ONE, 01 January 2015, Vol.10(3), p.e0120294 [Peer Reviewed Journal]

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  • Title:
    Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells
  • Author: Young Uk Kim ; Hoyong Lim ; Ha Eun Jung ; Rick A Wetsel ; Yeonseok Chung
  • Subjects: Sciences (General)
  • Is Part Of: PLoS ONE, 01 January 2015, Vol.10(3), p.e0120294
  • Description: BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1+ CXCR5+ Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5+ CD4+ T cells isolated from BXD2 mice induced the production of IgG from naïve B cells in an IL-21-dependent manner, while CCR6+ CD4+ T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice.
  • Language: English
  • Identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0120294

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