ILCs

Innate lymphoid cells (ILCs) are a family of immune cells derived from common lymphoid progenitors that inhabit tissues throughout the body, especially at barrier sites such as the gut, lungs, and skin. They lack rearranged antigen-specific receptors found on B and T cells, and they respond rapidly to cytokines and tissue-derived signals to shape early and ongoing immune responses. ILCs play a key role in maintaining tissue integrity and guiding subsequent adaptive immunity.

ILCs are commonly categorized into three main groups: ILC1, ILC2, and ILC3. ILC1 cells resemble TH1 responses and typically produce interferon-gamma (IFN-γ) in response to IL-12 and other signals, helping defend against intracellular pathogens. ILC2 cells resemble TH2 responses and secrete IL-4, IL-5, and IL-13, contributing to antiparasitic responses and allergic inflammation; they are activated by epithelial cytokines such as IL-33, IL-25, and TSLP. ILC3 cells resemble TH17/TH22 responses and produce IL-17 and/or IL-22, supporting mucosal defense against extracellular bacteria and shaping the epithelial barrier; they depend on the transcription factor RORγt. In many classifications, natural killer (NK) cells are considered part of the ILC family as group 1 ILCs, distinguished by cytotoxic activity. LTi (lymphoid tissue inducer) cells are an embryonic lineage of ILCs essential for the development of lymphoid organs.

Developmentally, ILCs arise from common lymphoid progenitors and differentiate under the influence of transcription factors such as T-bet (ILC1), GATA3 (ILC2), and RORγt (ILC3). They are responsive to tissue contexts and can exhibit plasticity between groups. Dysregulation of ILCs has been linked to infections, inflammatory diseases, allergies, and metabolic disorders, making them a focus of ongoing immunological research.