Characterization of NKp46+CCR6+ ILC3s in non-C57BL/6 mice 4352

Description Type 3 innate lymphoid cells produce cytokines that maintain intestinal epithelial cell homeostasis, initiate lymphoid tissue development, and enhance host defense mechanisms against extracellular pathogens. Here, we report an ILC3 phenotype characterized by co-expression of NKp46 and CCR6, which we observed in multiple inbred and outbred mouse strains but was notably absent in C57BL/6 mice. NKp46+CCR6+ ILC3s were present in intestinal lamina propria and were confirmed to be innate lymphocytes, developing in the absence of Rag1 but requiring the common gamma chain receptor subunit. Cultures of purified ILC3 subpopulations demonstrated that NKp46+CCR6+ cells were closely related to NKp46+CCR6- ILC3s, which was further confirmed in vivo by tracking adoptively transferred cells. Functionally, NKp46+CCR6+ ILC3s produced more IL-22 on a per cell basis than their NKp46+CCR6- counterparts during both homeostatic and infection conditions, indicating a heightened cell activation state in NKp46+CCR6+ cells. This study reveals an additional RORgt+ ILC3 phenotype, which may be tuned to meet the needs of the intestinal mucosa. Funding Sources Supported by NIH DK118110; T32GM00820; and the Donald E. and Delia B. Baxter Foundation. Topic Categories Mucosal and Regional Immunology (MUC)