Zfp362 potentiates murine colonic inflammation by constraining Treg cell function rather than promoting Th17 cell differentiation

Mucosal barrier integrity and pathogen clearance is a complex process influenced by both Th17 and Treg cells. Previously, we had described the DNA methylation profile of Th17 cells and identified Zinc finger protein (Zfp)362 to be uniquely demethylated. Here, we generated Zfp362(-/-) mice to unravel the role of Zfp362 for Th17 cell biology. Zfp362(-/-) mice appeared clinically normal, showed no phenotypic alterations in the T-cell compartment, and upon colonization with segmented filamentous bacteria, no effect of Zfp362 deficiency on Th17 cell differentiation was observed. By contrast, Zfp362 deletion resulted in increased frequencies of colonic Foxp3(+) Treg cells and IL-10(+) and ROR & gamma;t(+) Treg cell subsets in mesenteric lymph nodes. Adoptive transfer of naive CD4(+) T cells from Zfp362(-/-) mice into Rag2(-/-) mice resulted in a significantly lower weight loss when compared with controls receiving cells from Zfp362(+/+) littermates. However, this attenuated weight loss did not correlate with alterations of Th17 cells but instead was associated with an increase of effector Treg cells in mesenteric lymph nodes. Together, these results suggest that Zfp362 plays an important role in promoting colonic inflammation; however, this function is derived from constraining the effector function of Treg cells rather than directly promoting Th17 cell differentiation.

Automated summary

Zfp362 deficiency increases colonic inflammation but does not directly promote Th17 cell differentiation. Instead, it regulates the effector function of Treg cells, suggesting an important role in promoting colonic inflammation.