DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus.
Nat Commun
; 11(1): 4718, 2020 09 18.
Article
em En
| MEDLINE
| ID: mdl-32948777
ABSTRACT
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-κB pathways, and thus stimulates naïve 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
Tecido Adiposo
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Diabetes Mellitus Tipo 2
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Membro 25 de Receptores de Fatores de Necrose Tumoral
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article