Expansion of Interleukin-22-Producing Type 3 Innate Lymphoid Cells in the Gut of Tristetraprolin-Deficient Mice

Abstract

Tristetraprolin (TTP, encoded by Zfp36) is an RNA-binding protein that plays a major role in the control of inflammation. Zfp36^−/− mice spontaneously develop a complex multiorgan inflammatory syndrome but no overt intestinal inflammation, suggesting the involvement of local regulatory mechanisms. In this study, we observed local expansion of IL-22-producing type 3 innate lymphoid cells (ILC3s) in the lamina propria of Zfp36^−/− mice. Our findings demonstrate that this expansion was primarily influenced by cell-extrinsic cues. In the absence of IL-22, we observed delayed onset of arthritis in Zfp36^−/− mice but no clear evidence of exacerbated intestinal inflammation under steady-state conditions. However, we show that Zfp36^−/− mice were paradoxically protected from dextran sulfate sodium (DSS)-induced colitis and suggest that increased IL-22 production by ILC3 might contribute to this observation. Taken together, these data highlight the complex interplay between systemic inflammation and gut mucosal immune homeostasis.