Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response

Brian J. Laidlaw, Yisi Lu, Robert A. Amezquita, Jason S. Weinstein, Jason A. Vander Heiden, Namita T. Gupta, Steven H. Kleinstein, Susan M. Kaech, Joe Craft

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

CD4+ follicular regulatory T (Tfr) cells suppress B cell responses through modulation of follicular helper T (Tfh) cells and germinal center (GC) development. We found that Tfr cells can also promote the GC response through provision of interleukin-10 (IL-10) after acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of Treg cell–derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor Forkhead box protein 1 (FOXO1). IL-10 promoted nuclear translocation of FOXO1 in activated B cells. These data indicate that Tfr cells play a multifaceted role in the fine-tuning of the GC response and identify IL-10 as an important mediator by which Tfr cells support the GC reaction.

Original languageEnglish
Article numbereaan4767
JournalScience immunology
Volume2
Issue number16
DOIs
StatePublished - 2017
Externally publishedYes

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