Regnase-1 degradation is crucial for IL-33– and IL-25–mediated ILC2 activation

Regnase‐1–related endoribonucleases in health and immunological diseases

“…Additionally, Regnase-1 negatively regulates group 2 innate lymphoid cells (ILC2s) function, while IKK complex-mediated Regnase-1 degradation promotes the IL-33and IL-25-induced ILC2 activation. 54 Interestingly, Regnase-1 mRNA is targeted by Regnase-1 itself via a stem-loop region present in the Regnase-1 3′ UTR. 49 These findings show that as the IKK complex phosphorylates IκBα to activate transcription, it also phosphorylates Regnase-1 to release a "brake" on inflammatory mRNA expression.…”

RNA decay machinery safeguards immune cell development and immunological responses

“…ILC2 from mice ©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ 9 with a degradation-resistance mutation in REGNASE-1 showed reduced expression of IL-33-inducing mRNAs, compared to wild-type ILC2 [83]. Moreover, bleomycin-induced pulmonary fibrosis in lymphocyte-deficient mice was more severe when ILC2 from Zc3h12a-deficient mice was transferred, compared with wild-type ILC2 transfer [84].…”

Group 2 innate lymphoid cells (ILC2s): The spotlight in asthma pathogenesis and lung tissue injury

“…71 IL-33, or IL-2/33, is a potent activator of ILC2, resulting in enhanced production of critical effector cytokines IL-5 and IL-13, which are responsible for the development of allergic airway inflammation. 72,73 On the other hand, IL-33-deficient mice have impaired AHR, and mice deficient in IL-33 receptor, ST2 mice have declined parasitic expulsion. 69 On the contrary, other cytokines have shown to inhibit mouse and human ILC2 responses, such as IFN-beta, IL-10, TGF-beta, IFNgamma, and IL-27.…”