| First Author | Shafiei-Jahani P | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 4718 |
| PubMed ID | 32948777 | Mgi Jnum | J:296771 |
| Mgi Id | MGI:6469793 | Doi | 10.1038/s41467-020-18601-7 |
| Citation | Shafiei-Jahani P, et al. (2020) DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus. Nat Commun 11(1):4718 |
| abstractText | Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-kappaB pathways, and thus stimulates naive and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM. |
