| First Author | Wang A | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 2 | PubMed ID | 33355624 |
| Mgi Jnum | J:306129 | Mgi Id | MGI:6509831 |
| Doi | 10.1084/jem.20201217 | Citation | Wang A, et al. (2021) ZFP91 is required for the maintenance of regulatory T cell homeostasis and function. J Exp Med 218(2) |
| abstractText | Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell-specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis. TCR-triggered autophagy induction largely relied on T reg cell-derived ZFP91 to restrict hyperglycolysis, which is required for the maintenance of T reg cell homeostasis. Mechanistically, ZFP91 rapidly translocated from the nucleus to the cytoplasm in response to TCR stimulation and then mediated BECN1 ubiquitination to promote BECN1-PIK3C3 complex formation. Therefore, our results highlight a ZFP91-dependent mechanism promoting TCR-initiated autophagosome maturation to maintain T reg cell homeostasis and function. |
