Posttranscriptional regulation of ILC2 homeostatic function via tristetraprolin
Open Access
- 28 October 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (12)
- https://doi.org/10.1084/jem.20210181
Abstract
Group 2 innate lymphoid cells (ILC2s) are unique in their ability to produce low levels of type 2 cytokines at steady state, and their production capacity is dramatically increased upon stimulation with IL-33. However, it is unknown how constitutive cytokine production is regulated in the steady state. Here, we found that tristetraprolin (TTP/Zfp36), an RNA-binding protein that induces mRNA degradation, was highly expressed in naive ILC2s and was downregulated following IL-33 stimulation. In ILC2s from Zfp36−/− mice, constitutive IL-5 production was elevated owing to the stabilization of its mRNA and resulted in an increased number of eosinophils in the intestine. Luciferase assay demonstrated that TTP directly regulates Il5 mRNA stability, and overexpression of TTP markedly suppressed IL-5 production by ILC2s, even under IL-33 stimulation. Collectively, TTP-mediated posttranscriptional regulation acts as a deterrent of excessive cytokine production in steady-state ILC2s to maintain body homeostasis, and downregulation of TTP may contribute to massive cytokine production under IL-33 stimulation.Funding Information
- Japan Society for Immunology
- Japan Society for the Promotion of Science (18K07187, 16K15362, 18H05286)
- Japan Agency for Medical Research and Development (16ek0410031h0001)
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