| First Author | Poholek AC | Year | 2016 |
| Journal | Sci Immunol | Volume | 1 |
| Issue | 5 | PubMed ID | 28713870 |
| Mgi Jnum | J:361201 | Mgi Id | MGI:7856574 |
| Doi | 10.1126/sciimmunol.aaf8612 | Citation | Poholek AC, et al. (2016) IL-10 induces a STAT3-dependent autoregulatory loop in T(H)2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes. Sci Immunol 1(5):eaaf8612 |
| abstractText | 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 (T(H)2) 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 T(H)2 cells. Furthermore, we found that the cytokine interleukin-10 (IL-10) acted directly on T(H)2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in T(H)2 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 T(H)2 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. |
