Paneth Cells Regulates Innate Lymphoid Cells and B1 Cells Throughout the Body

Paneth cells are a subset of small intestinal epithelial cells specialized to maintain gastrointestinal homeostasis through production of antimicrobial products and cytokines. The fact that dysbiosis has been associated with several noninfectious pathologies, has solidified the notion that Paneth cells contribute to the general health. However, little is known about Paneth cells beyond their role as regulator of the gut microbiota. Using mice lacking Paneth cells (Sox9 ΔIECmice), we now report that Paneth cells also regulate the composition of immune cell subsets in Gut-Associated Lymphoid Tissues (GALT) and but also in sites distant from the gut. Thus, loss of Paneth cells significantly decreased the number of ILC3s and increased the number of ILC2s in the intestinal lamina propria. Paneth cell deficiency also affected Peyer’s patches. In this regard, Paneth cell deficient mice displayed an increased numbers of Peyer’s patches which were of larger size than Peyer’s patches in control wild-type mice. Furthermore, Peyer’s patches of Paneth cell deficient mice contained increase numbers of IgA +CD19 +B cells and B1a (CD19 +CD5 +) cells. Interestingly, when compared to control wild-type mice, the numbers of B1a cells were found to be also increased in mesenteric lymph nodes of Paneth cell deficient mice, but also at sites distant from the gut including the lungs, and bone marrow. Also, in the lungs there was an increase in ILC2s. Taken together, these findings indicate that Paneth cells play a key role as regulators of innate immune responses throughout the body via regulation of ILC subsets and B1 cells. NIH Grants