| First Author | Mori T | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 7 | Pages | 1830-1841 |
| PubMed ID | 30110639 | Mgi Jnum | J:271115 |
| Mgi Id | MGI:6278438 | Doi | 10.1016/j.celrep.2018.07.036 |
| Citation | Mori T, et al. (2018) Lnk/Sh2b3 Regulates Adipose Inflammation and Glucose Tolerance through Group 1 ILCs. Cell Rep 24(7):1830-1841 |
| abstractText | Lnk/Sh2b3 is an adaptor protein that negatively regulates cytokine signaling in lymphohematopoiesis. A missense variant within the LNK/SH2B3 gene has been reported to be a risk variant for several autoimmune diseases, including diabetes. We found that glucose tolerance and insulin responses were impaired in Lnk(-/-) mice. Moreover, immune cells such as group 1 innate lymphoid cells (G1-ILCs), CD8(+) T cells, and M1 macrophages accumulated in adipose tissue. When Lnk(-/-) mice were crossed with Il15(-/-) mice or depleted of G1-ILCs but not CD8(+) T cells, glucose intolerance and adipose inflammation were ameliorated. Lnk(-/-) G1-ILCs showed activated phenotypes as well as enhanced reactivity for IL-15, and administration of a JAK inhibitor improved glucose tolerance. Accordingly, a high-fat diet greatly worsened glucose intolerance in Lnk(-/-) mice. Thus, Lnk/Sh2b3 controls homeostasis in adipose tissue and reduces the risk of onset of diabetes by regulating the expansion and activation of IL-15-dependent adipose G1-ILCs. |
