Innate Lymphoid Cells

Innate lymphoid cells (ILCs) are a recently identified immune cell type that is found in almost every tissue but is specifically enriched at mucosal surfaces, where they are thought to play an important role in maintaining epithelial barrier integrity and regulating immune responses. Several subsets of ILCs have been characterized based on differences in their phenotypes and functional properties. These include group 1 ILCs, which consist of natural killer cells (NK cells) and ILC1 cells, group 2 ILCs (ILC2s), and a heterogeneous population of group 3 ILCs (ILC3s), which includes (NCR+) ILC3s, (NCR-) ILC3s, and fetal lymphoid tissue-inducer cells (LTi cells). ILCs develop from a common lymphoid progenitor (CLP) that originates in the fetal liver or bone marrow. This cell gives rise to a NK cell precursor and a common helper-like innate lymphoid precursor (CHILP), from which a PLZF+ common ILC precursor (ILCP) and a LTi progenitor cell are derived. The LTi progenitor cell gives rise to LTi cells, while the PLZF+ ILCP gives rise to the cells belonging to the ILC1, ILC2, and ILC3 subsets, with the exception of LTi cells. Although ILCs lack rearranged antigen receptors, each of these groups of ILCs is considered to be the innate counterpart of a corresponding adaptive helper T cell subset due to similarities in the transcription factors that direct their development, their cytokine expression profiles, and their functions. Group 1 ILCs, including NK cells and ILC1s, are involved in mediating the immune response against intracellular viral and bacterial pathogens. NK cells have been suggested to be the innate equivalent of CD8+ T cells as both NK and CD8+ T cells express the transcription factors, T-bet and Eomes, secrete IFN-gamma, and have cytotoxic functions. In contrast, ILC1s are thought to be the innate counterpart of Th1 cells as both of these cell types express T-bet and secrete IFN-gamma. Similarly, ILC2s, which express the transcription factor, GATA-3, and produce Th2-like cytokines in response to large extracellular pathogens have been suggested to be the innate equivalent of Th2 cells, while ILC3s, which require ROR gamma t for their development, produce Th17- and Th22-like cytokines, and are required for host defense against extracellular bacteria and fungi, are considered to be the innate equivalent of Th17 and Th22 cells.