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

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Science Immunology  20 Oct 2017:
Vol. 2, Issue 16, eaan4767
DOI: 10.1126/sciimmunol.aan4767

Probing the functions of follicular regulatory T cells

CD4+ follicular regulatory T (Tfr) cells express key molecules that are associated with regulatory T cell and follicular helper T cell functions. Although it is known that Tfr cells produce interleukin-10 (IL-10), it has been unclear whether IL-10 production by these cells regulates germinal center (GC) responses in vivo. By specifically ablating IL-10 expression in murine Tfr cells, Laidlaw et al. demonstrate that Tfr cell–derived IL-10 does support GC responses in the context of acute viral infection. They found dendritic cells and B cells in the GCs to be IL-10–responsive and showed that IL-10 promoted GC B cells to adopt a dark zone phenotype.


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.

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