Katsuhide Okunishi1,2*, Yuta Kochi3, Min Zhao1, Hao Wang1, Kazuyuki Nakagome4, Tetsuro Izumi1* (1. Laboratory of Molecular Endocrinology and Metabolism, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University. 2. Laboratory of Endocrine and Metabolic System Regulation, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University. 3. Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University. 4. Department of Respiratory Medicine, Saitama Medical University; *Corresponding Authors)
About
Recently, common risk variants in the UNC13D gene were found by genome-wide association studies of asthma and obesity. Munc13-4, encoded by the UNC13D gene is known to regulate cytotoxic granule secretion, although its role in allergy and obesity remains unclear. In the present study, we investigated the physiological roles of Munc13-4 in mouse models of both asthma and metabolic disorders using Munc13-4 deficient Jinx mice. Systemic Munc13-4 deficiency in Jinx mice exacerbated both allergic lung inflammation and HFD-induced obesity/diabetes. Mechanistically, Munc13-4 deficiency impaired secretion of immunoregulatory cytokines IL-10 and IL-12 by CD11c+ antigen presenting cells, which enhanced allergic lung inflammation and chronic inflammation in adipose tissues under HFD condition, the latter of which further resulted in the exacerbation of obesity and diabetes. This is the first study to describe such regulatory roles of Munc13-4 in both allergic and metabolic immune responses, and provides new insights into their common pathophysiology.
Paper information
Okunishi K, Kochi Y, Zhao M, Wang H, Nakagome K, Izumi T. Munc13-4 regulates asthma and obesity in mice by controlling functions of CD11c+ antigen-presenting cells. Allergy. 2024. Online ahead of print. https://doi.org/10.1111/all.16087
