Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells
By A. Fuchs, W. Vermi, Jacob S. Lee, S. Lonardi, S. Gilfillan, R. Newberry, M. Cella, M. Colonna. 2013
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Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced Interferon-γ in response to IL-12 and IL-15, had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting and a memory-activated phenotype. Because tissue-resident memory CD8+ T cells share this profile, intraepithelial ILC1 may be their innate counterparts. In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3-and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are distinct from conventional NK cells. Intraepithelial ILC1 were amplified in Crohn’s disease patients and contributed to pathology in the anti-CD40-induced colitis model in mice. Thus, intraepithelial ILC1 may initiate interferon-γ responses against pathogens, but contribute to pathology when dysregulated.
Subfields: Immunology, Surgery
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In Immunology
Citations in the corpus
- Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “which are found in increased abundance in the intestine of IBD patients (Fuchs et al., 2013; Geremia et al., 2011), can contribute to the production of colitogenic effector cytokines”
- Natural killer cells in cancer biology and therapy (2020, background): “Although ILC1s are not detectable in many tissues, intra-epithelial ILC1 (ieILC1)-like cells, which highly express IFN-γ, integrins and other cytotoxic molecules similar to the ieILC1s previously described by Fuchs except for different NKp44 expression, could represent the majority of NK cells in th”