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


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.

SUBMITTER: Laidlaw BJ 

PROVIDER: S-EPMC5846620 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Interleukin-10 from CD4<sup>+</sup> follicular regulatory T cells promotes the germinal center response.

Laidlaw Brian J BJ   Lu Yisi Y   Amezquita Robert A RA   Weinstein Jason S JS   Vander Heiden Jason A JA   Gupta Namita T NT   Gupta Namita T NT   Kleinstein Steven H SH   Kaech Susan M SM   Craft Joe J  

Science immunology 20171001 16


CD4<sup>+</sup> follicular regulatory T (T<sub>fr</sub>) cells suppress B cell responses through modulation of follicular helper T (T<sub>fh</sub>) cells and germinal center (GC) development. We found that T<sub>fr</sub> 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 T<su  ...[more]

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