Expansion of Interleukin-22-producing Innate Lymphoid Cells in Tristetraprolindeficient mice protects against Dextran Sulfate Sodium-induced Colitis

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 multi-organ inflammatory syndrome that shares many features with spondyloarthritis. Herein, we show that Zfp36 -/-mice are paradoxically protected from Dextran Sulfate Sodium (DSS)-induced colitis. This effect was maintained on a Rag2 -/- background but was lost in Rag2 -/-Il2rg -/-Zfp36 -/-mice that lack innate lymphoid cells (ILCs). Furthermore, we observed a local expansion of type 3 ILCs in the lamina propria of Zfp36 -/-mice. These cells produced large amounts of Interleukin (IL)-22 and were expanded in response to systemic inflammation. Finally, we show that IL-22 contributed to protection of Zfp36 -/-mice against DSSinduced colitis but had a minor impact on their spontaneous inflammatory syndrome. Taken together, these data highlight the complex role of TTP in the control of organ-specific inflammation. Overall design: Zfp36-deficient mice (Zfp36-/-), LoxP-flanked Zfp36 mice (Zfp36 flox/flox) and Zfp36-V5 knock-in mice on a C57BL/6 background were used to assess inflammatory response mediated by innate lymphoid cells (ILCs).