Loss of Paneth cells alters intestinal innate lymphoid cells and enhances weight gain in mice

• Published in: The Journal of immunology (1950) 2022-05, Vol.208 (1_Supplement), p.171-171.16
• Main Authors: Joldrichsen, Marisa R, Kim, Eunsoo, Steiner, Haley E, Cormet-Boyaka, Estelle, Boyaka, Prosper N
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.171.16

Paneth cells are a subset of small intestinal epithelial cells specialized in the production of antimicrobial products and cytokines. Gastrointestinal dysbiosis has been linked to many health concerns and is believed to be a contributing factor in obesity. Despite the role of Paneth cells as a major source of antimicrobial products, the contribution of these cells to health or disease conditions has not been fully explored. We examine the impact loss of Paneth cells would have on the gut microbiota and whether the subsequent dysbiosis could affect metabolic functions of the host and fat accumulation in a mouse model of diet induced obesity. For this purpose, were used wild-type and Sox9ΔIEC mice, which lack Paneth cells due to a Sox9 gene deletion within the intestinal epithelium. Compared to control wild-type mice, the small intestine of Sox9ΔIEC exhibited an altered profile of ILCs characterized by increase ILC2 and decrease ILC3 numbers. After exposure to a high-fat diet for 13 weeks, the Sox9ΔIEC mice gained more weight and had higher glucose intolerance. The intestinal homeostasis was also affected, with an increase in intestinal permeability and an increase in ILC1s within the small intestine of Sox9ΔIEC mice. In the abdominal fat Sox9ΔIEC mice showed increased numbers of immune cells including inflammatory macrophages, T cells, and B cells. Finally, fecal material transplantation experiments revealed that fecal material from the Sox9ΔIEC mice transfer the phenotype in recipient germ-free mice as indicated by a trend towards an increase in weight gain and immune cell infiltration of abdominal fat. These results highlight the importance of Paneth cells as regulators of metabolic functions of the host and fat accumulation. Supported by grants from OSU and NIH.