Posttranscriptional regulation of ILC2 homeostatic function via tristetraprolin
| Autor: | Yuki Hikichi, Osamu Takeuchi, Kazuyo Moro, Yasutaka Motomura |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Immunology Tristetraprolin Stimulation Downregulation and upregulation medicine Immunology and Allergy ZFP36 Animals Homeostasis Lymphocytes RNA Messenger RNA Processing Post-Transcriptional Interleukin-13 Chemistry Innate lymphoid cell Interleukin-33 Immunity Innate Mice Mutant Strains Cell biology Interleukin 33 DNA-Binding Proteins Mice Inbred C57BL Cytokine Interleukin 13 Cytokines Female Interleukin-5 Interleukin Receptor Common gamma Subunit |
| Zdroj: | The Journal of experimental medicine. 218(12) |
| ISSN: | 1540-9538 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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