Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production

Dalmas et al., 2017, Immunity 47, 928–942

Speaker: Sung-Lin Liu (劉松林)                                   Time: 13:10~14:00, May. 2.2018

Commentator: Dr. Pin Ling (凌斌 老師)          Place: Room 601

Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during type 2 diabetes.  Recent studies suggest that alternatively activated macrophages, regulatory T cells, eosinophil, and group 2 innate lymphoid cells (ILC2s) reside in the pancreatic tissue and contribute the inflammation.  Moreover, retinoic acid (RA) produced by myelid cells is very important to enhance type 2 immune responses.  However, how the immune system of the pancreatic islets contributes to the maintenance of β cell function that remains unknown.  Therefore, the authors hypothesized that islet-resident ILC2s promote insulin secretion in diabetes.  First, the authors investigated the glucose tolerance and type 2 immunity in the mice islet with different genetic backgrounds.  The authors found higher IL-33 and insulin production in the islets of Th2-cell-permissive BALB/c mouse when compared with the islets of Th1-cell-permissive C57BL/6 mouse.  Second, the authors investigated the effect of IL-33 signaling in β cell function in the islets of WT mice and Rag2^-/-  Il2rg^-/- mice.  The authors found that IL-33 enhanced the glucose-stimulated insulin secretion in WT mice but not in Rag2^-/- Il2rg^-/- mice.  Third, the authors investigated whether IL-33-ILC2 axis depend on RA.  The authors found that IL-33 enhanced insulin production in islets macrophages and islets dendritic cells in normal chow diet mice but not in vitamin-A-deprived mice.  The authors hence concluded that IL-33 enhances RA produced from ILC2s-stimulated-myeloid cell that promotes β cell function.  Activation of IL33-ILC2-meyloid axis could enhance the insulin production of β cell and reduce inflammation in the islet.  The new pathway discovered in this study may offer novel approaches for diabetes treatment.

References:

1.  Donath, M.Y., Dalmas, E´ ., Sauter, N.S., and Bo¨ ni-Schnetzler, M. (2013).

Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity.

Cell Metab. 17, 860–872.

2. Odegaard, J.I., and Chawla, A. (2015). Type 2 responses at the interface between

immunity and fat metabolism. Curr. Opin. Immunol. 36, 67–72.