| First Author | Dalmas E | Year | 2017 |
| Journal | Immunity | Volume | 47 |
| Issue | 5 | Pages | 928-942.e7 |
| PubMed ID | 29166590 | Mgi Jnum | J:254529 |
| Mgi Id | MGI:6111920 | Doi | 10.1016/j.immuni.2017.10.015 |
| Citation | Dalmas E, et al. (2017) Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production. Immunity 47(5):928-942.e7 |
| abstractText | Pancreatic-islet inflammation contributes to the failure of beta cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1beta, and palmitate). IL-33 promoted beta cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In turn, local RA signaled to the beta cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute beta cell stress but was defective during chronic obesity. Accordingly, IL-33 injections rescued islet function in obese mice. Our findings provide evidence that an immunometabolic crosstalk between islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion. |
