Dectin-2 Deficiency Promotes Proinflammatory Cytokine Release From Macrophages and Impairs Insulin Secretion

Masamichi Fujita, Takashi Miyazawa, Keiichiro Uchida, Naohiro Uchida, Shojiro Haji, Seiichi Yano, Norifusa Iwahashi, Tomomi Hatayama, Shunsuke Katsuhara, Shintaro Nakamura, Yukina Takeichi, Maki Yokomoto-Umakoshi, Yasutaka Miyachi, Ryuichi Sakamoto, Yoichiro Iwakura, Yoshihiro Ogawa
Endocrinology, Volume 165, Issue 1, January 2024, bqad181
https://doi.org/10.1210/endocr/bqad181

Abstract

Pancreatic islet inflammation plays a crucial role in the etiology of type 2 diabetes (T2D). Macrophages residing in pancreatic islets have emerged as key players in islet inflammation. Macrophages express a plethora of innate immune receptors that bind to environmental and metabolic cues and integrate these signals to trigger an inflammatory response that contributes to the development of islet inflammation. One such receptor, Dectin-2, has been identified within pancreatic islets; however, its role in glucose metabolism remains largely unknown. Here we have demonstrated that mice lacking Dectin-2 exhibit local inflammation within islets, along with impaired insulin secretion and β-cell dysfunction. Our findings indicate that these effects are mediated by proinflammatory cytokines, such as interleukin (IL)-1α and IL-6, which are secreted by macrophages that have acquired an inflammatory phenotype because of the loss of Dectin-2. This study provides novel insights into the mechanisms underlying the role of Dectin-2 in the development of islet inflammation.

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