Distinct requirements for T-bet in gut innate lymphoid cells

Abstract

The transcription factor T-bet drives the differentiation of NKp46-expressing IL-22–producing innate lymphoid cells

Interleukin‐23 Mediates the Intestinal Response to Microbial β‐1,3‐Glucan and the Development of Spondyloarthritis Pathology in SKG Mice

“…IL-22 production by intestinal IL-22-producing innate lymphoid cells is T-bet dependent and signaled by microbiota (36)(37)(38). Consistent with this, IL-22ϩNKp44ϩ cells with possible gut-protective function in humans were reduced in Crohn's disease patients and increased in the ileum of AS patients without clinical IBD (39).…”

Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet−/−.Rag2−/−(TRUC) mice

“…While NKp46 + IL-22 secreting ILCs have been demonstrated to require T-bet for development (31,32), we show that T-bet also controls IL-17A induction in a subset of Thy1 hi NKp46 − RORγt + ILCs. The inhibitory effect of T-bet on IL-17A secretion by ILCs is not sufficiently explained by suppression of RORγt (43) as RORγt expression levels in RORγt-positive ILCs from Rag2 −/− and TRUC mice are similar (Fig.…”

“…S3G). T-bet has been shown to be required for the differentiation of NKp46 + ILCs (31,32). Our data demonstrate that T-bet also controls the function of Thy1 hi NKp46 − ILCs, suggesting that enhanced IL-17A secretion by T-bet-deficient ILCs is a key factor in TRUC pathogenesis.…”

“…T-bet controls the phenotype of several innate immune cell types including dendritic cells (1), NK cells (42), and RORγt + innate lymphoid cells (31,32). While NKp46 + IL-22 secreting ILCs have been demonstrated to require T-bet for development (31,32), we show that T-bet also controls IL-17A induction in a subset of Thy1 hi NKp46 − RORγt + ILCs.…”

Validation of Intratumoral T-bet+ Lymphoid Cells as Predictors of Disease-Free Survival in Breast Cancer

“…While recognition of the individual immune cell subsets that consistently mediate favorable effects remains elusive, the current consensus is that CD4 þ Th1 and CD8 þ T cells are among the players that can generate effective although potentially attenuated antitumor responses while CD4 þ Th2 cells and CD4 þ Tregs are among the cells that can suppress antitumor immunity and can promote tumor progression (14)(15)(16). T-bet (T-box transcription factor 21), an immune cell-specific member of the T-box family of transcription factors, is expressed in multiple cells of the innate and adaptive immune system [including dendritic cells, natural killer (NK) cells, CD4 þ and CD8 þ effector cells, B cells, and a subset of regulatory T cells], and its expression is required for the survival, development, and proper functioning of immune cells (17)(18)(19)(20)(21)(22)(23). In disease states, T-bet plays an important role in infectious and inflammatory conditions as well as in tumor progression: in the absence of Tbet, susceptibility to metastases from melanoma was shown to be increased because of impaired NK-cell function and survival in vivo (24).…”