Foxp3+ T cells expressing RORγt represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation

Differential expression of GPR15 on T cells during ulcerative colitis

“…Recently, GPR15 was shown to be expressed on murine and human CD4 + T cell subsets and to be highly involved in their trafficking to the colon (12,13 (20,21). Well in line with this, we identified that the differential cytokine profile of GPR15 + CD4 + T cells is not restricted to healthy individuals but is also detectable in the blood of UC patients, providing evidence that the subset of GPR15 + T cells might have proinflammatory and antiinflammatory properties, depending on the cell type and the microenvironment.…”

Microbiota, regulatory T cell subsets, and allergic disorders

“…Furthermore, Gata3 expression in Tregs is necessary for prevention of a spontaneous in ammatory disorder and e ective suppression of a transfer colitis [76,77]. However, ROR(γt) + Tregs have been shown to protect more e ciently than ROR(γt) − Tregs in this transfer colitis model [67] raising the question of whether both subsets use di erent mechanisms to suppress T cell proliferation in a lymphopenic environment. Two observations make it unlikely that Gata3 + Tregs are induced upon recognition of foreign antigens/allergens: rstly, Gata3 + Tregs do at least to a certain degree express Helios (and may thus be rather of thymic origin and/or recognize self antigens) and secondly, Gata3 + Tregs can still be found in germfree mice [60] (Fig.…”

“…Constitutive ablation of dendritic cells has been previously associated with failed central tolerance induction and thus autoimmunity but not with failed Treg induction [68]. Importantly, ROR(γt) + -Tregs show a stable phenotype in vitro and in vivo and also have a fully demethylated TSDR (Treg-speci c demethylated region) of the Foxp3 promoter and other key regulatory molecules [67]. erefore, one can expect that ROR(γt) + Tregs are rather stable and execute an important regulatory function in the gut at steady state.…”

“…Only few ROR(γt) + Foxp3 + Tregs are directly generated from ex 17 cells [67,71]. is may re ect the circumstance that a massive expansion of 17 cells during in ammation occurs and only a limited niche for Tregs exists to enable tolerance to symbiotic microbes.…”

“…Others and we have now shown that these ROR(γt) + Tregs represent a stable population of Tregs that exert a critical regulatory function in the gut [59,60,67]: rstly, the highest frequency of ROR(γt) + Tregs can be found in the intestinal lamina propria of mice a er weaning and their frequency seems to correlate with the bacterial load (and thus possibly with antigen exposure) because their frequency increases from esophagus to small intestine to colon.…”