| First Author | Kang YH | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 912 |
| PubMed ID | 30796216 | Mgi Jnum | J:283027 |
| Mgi Id | MGI:6286772 | Doi | 10.1038/s41467-019-08743-8 |
| Citation | Kang YH, et al. (2019) STAT1 signaling shields T cells from NK cell-mediated cytotoxicity. Nat Commun 10(1):912 |
| abstractText | The JAK-STAT pathway critically regulates T-cell differentiation, and STAT1 is postulated to regulate several immune-mediated diseases by inducing proinflammatory subsets. Here we show that STAT1 enables CD4(+) T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination. Stat1(-/-) T cells fail to expand and establish colitis in lymphopenic mice. This defect is not fully recapitulated by the combinatorial loss of type I and II IFN signaling. Mechanistically, Stat1(-/-) T cells have reduced expression of Nlrc5 and multiple MHC class I molecules that serve to protect cells from NK cell-mediated killing. Consequently, the depletion of NK cells significantly rescues the survival and spontaneous proliferation of Stat1(-/-) T cells, and restores their ability to induce colitis in adoptive transfer mouse models. Stat1(-/-) mice however have normal CD4(+) T cell numbers as innate STAT1 signaling is required for their elimination. Overall, our findings reveal a critical perspective on JAK-STAT1 signaling that might apply to multiple inflammatory diseases. |
