NCR-ILC3

Natural cytotoxicity receptor (NCR)- group 3 innate lymphoid cells (ILC3s) are a subset of innate lymphoid cells (ILCs) that includes both fetal lymphoid tissue inducer (LTi) cells and postnatal LTi-like ILC3s. This subset, along with (NCR)+ ILC3s, are the two ILC3 subsets that have been characterized in both mice and humans. After birth, both (NCR)- and (NCR)+ ILC3s are thought to contribute to the immune response against specific extracellular pathogens and the maintenance of tissue homeostasis at mucosal sites. The (NCR)- ILC3 subset also includes fetal lymphoid tissue inducer (LTi) cells, which are required for the development of secondary lymphoid organs during embryogenesis. Both (NCR)- and (NCR)+ ILC3s require the transcription factor, ROR gamma t for their development, and produce IL-22 and/or IL-17 following activation. Additionally, both ILC3 subsets are activated by IL-23, IL-1 alpha, IL-1 beta, IL-7, TL1A, and Prostaglandin E2 (PGE2). (NCR)- ILC3s are considered to be the innate equivalent of Th17 cells, while (NCR)+ ILC3s have been suggested to be the innate equivalent of Th22 cells. In mice, (NCR)- ILC3s produce both IL-17 and IL-22, and can be identified by the expression of CCR6, CD90/Thy1, CD117/c-kit, CD127/IL-7 R alpha, coupled with the lack of expression of NKp46 and lineage markers (Lin-) that are commonly used to identify other immune cell types. In contrast, both the (NCR)- and (NCR)+ ILC3 subsets in humans express CCR6. As a result, human (NCR)- ILC3s are typically identified based on their expression of CD117/c-kit and CD127/IL-7 R alpha, and their lack of expression of NKp44, NKp46, NCAM-1/CD56, and lineage markers. Unlike the mouse ILC3 subsets, IL-22 production by human ILC3s is restricted to the (NCR)+ ILC3 subset, while human (NCR)- ILC3s predominantly produce IL-17.