Intraepithelial Type 1 Innate Lymphoid Cells Are a Unique Subset of IL-12- and IL-15-Responsive IFN-γ-Producing Cells

Abstract

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.

Innate Lymphoid Cells in Graft-Versus-Host Disease

“…This cytotoxic ILC1 subset exists in mouse as well, where it was found to express CD160 and NKp46 but not CD103. Furthermore, this subset was NFIL‐3‐, and T‐bet‐dependent and IL‐15‐responsive 11. Importantly, these cells, although cytotoxic, were shown to be distinct from NK cells as they also developed in il15r −/− mice lacking NK cells.…”

“…Both CD127 − and CD127 + ILC1 are highly accumulated in the inflamed ileum of Crohn's disease patients, potentially contributing to the pathogenesis of gut inflammation 11, 12.…”

Les cellules lymphoïdes innées

“…Notamment, comment une population lymphocytaire intestinale et intra-épi-théliale n'exprimant pas de récepteur de l'antigène se développe chez la souris et chez l'homme indépendamment du facteur de transcription Id2 qui est pourtant essentiel à la différenciation des ILC [32]. De plus, chez l'homme, une population intra-épithéliale d'ILC1, qui exprime Eomes, T-bet et CD103, reste, encore aujourd'hui, sans précurseur identifié [33].…”

“…Ces 3), PLZF (promyelocytic leukaemia zinc finger), T-bet (T-box transcription factor), Eomes (Eomesodermin), RUNX3 (runt-related transcription factor 3), ROR (RAR-related orphan receptor a), Bcl11b (B-cell lymphoma/leukemia 11B), Gfi1 (growth factor independent 1), RORt (RAR-related orphan receptor gt), AhR (Aryl hydrocarbon receptor). Il a été montré chez l'homme que les ILC1 peuvent provenir de précurseurs autres que les ILCP mais qui restent pour l'instant inconnus [33]. Il est indiqué, pour chaque population d'ILC, les principales molécules effectrices qui peuvent être produites après activation.…”

“…Les ILC1 Les patients atteints de la maladie de Crohn ou d'une broncho-pneumopathie chronique obstructive (BPCO) présentent respectivement une fréquence plus importante d'ILC1 dans les intestins et les poumons [17,33]. Bien que les ILC1 puissent protéger l'organisme de certaines colites, l'IFN- qu'elles produisent participe égale-ment au développement de celles induites par Helicobacter hepaticus [46].…”