| First Author | Mikami Y | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 3 | Pages | 514-525.e6 |
| PubMed ID | 33657395 | Mgi Jnum | J:305774 |
| Mgi Id | MGI:6706475 | Doi | 10.1016/j.immuni.2021.02.015 |
| Citation | Mikami Y, et al. (2021) MicroRNA-221 and -222 modulate intestinal inflammatory Th17 cell response as negative feedback regulators downstream of interleukin-23. Immunity 54(3):514-525.e6 |
| abstractText | MicroRNAs are important regulators of immune responses. Here, we show miR-221 and miR-222 modulate the intestinal Th17 cell response. Expression of miR-221 and miR-222 was induced by proinflammatory cytokines and repressed by the cytokine TGF-beta. Molecular targets of miR-221 and miR-222 included Maf and Il23r, and loss of miR-221 and miR-222 expression shifted the transcriptomic spectrum of intestinal Th17 cells to a proinflammatory signature. Although the loss of miR-221 and miR-222 was tolerated for maintaining intestinal Th17 cell homeostasis in healthy mice, Th17 cells lacking miR-221 and miR-222 expanded more efficiently in response to IL-23. Both global and T cell-specific deletion of miR-221 and miR-222 rendered mice prone to mucosal barrier damage. Collectively, these findings demonstrate that miR-221 and miR-222 are an integral part of intestinal Th17 cell response that are induced after IL-23 stimulation to constrain the magnitude of proinflammatory response. |
