Research ArticleAUTOIMMUNITY

IL-10 induces a STAT3-dependent autoregulatory loop in TH2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes

See allHide authors and affiliations

Science Immunology  11 Nov 2016:
Vol. 1, Issue 5, eaaf8612
DOI: 10.1126/sciimmunol.aaf8612

You are currently viewing the abstract.

View Full Text

Regulating Blimp-1 in TH2 cells

The transcription factor Blimp-1 has been reported to limit autoimmunity in T cells. Now, Poholek et al. explore the mechanisms regulating Blimp-1 expression in T helper 2 (TH2) cells. They found that the cytokine interleukin-10 (IL-10) induced Blimp-1 expression in TH2 cells through STAT3. Signal transducer and activator of transcription 3 (STAT3) and Blimp-1 then acted together to boost IL-10 expression in a positive regulatory loop. The induced Blimp-1 then limited cell expansion by inhibiting STAT5 induction of cell cycle and antiapoptotic genes. Thus, by activating Blimp-1, IL-10 may prevent cell expansion, thus restraining autoimmunity.

Abstract

Blimp-1 expression in T cells extinguishes the fate of T follicular helper cells, drives terminal differentiation, and limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in T helper 2 (TH2) cells and the molecular basis of its actions. We report that signal transducer and activator of transcription 3 (STAT3) unexpectedly played a critical role in regulating Blimp-1 in TH2 cells. Furthermore, we found that the cytokine interleukin-10 (IL-10) acted directly on TH2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in TH2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and antiapoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in TH2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity.

View Full Text