Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression.

Autor: Bataclan M; https://ror.org/05gfswd81 Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Leoni C; https://ror.org/05gfswd81 Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Moro SG; https://ror.org/05gfswd81 Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Pecoraro M; https://ror.org/05gfswd81 Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland., Wong EH; Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich, Planegg-Martinsried, Germany., Heissmeyer V; Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich, Planegg-Martinsried, Germany.; Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Munich, Germany., Monticelli S; https://ror.org/05gfswd81 Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland silvia.monticelli@irb.usi.ch.
Jazyk: angličtina
Zdroj: Life science alliance [Life Sci Alliance] 2024 Jun 03; Vol. 7 (8). Date of Electronic Publication: 2024 Jun 03 (Print Publication: 2024).
DOI: 10.26508/lsa.202402784
Abstrakt: Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) impacts immune cell responses, including mast cell functionality. Despite their importance in immune regulation, the functional role of most RBPs remains to be understood. By manipulating the expression of specific RBPs in murine mast cells, coupled with mass spectrometry and transcriptomic analyses, we found that the Regnase family of proteins acts as a potent regulator of mast cell physiology. Specifically, Regnase-1 is required to maintain basic cell proliferation and survival, whereas both Regnase-1 and -3 cooperatively regulate the expression of inflammatory transcripts upon activation, with Tnf being a primary target in both human and mouse cells. Furthermore, Regnase-3 directly interacts with Regnase-1 in mast cells and is necessary to restrain Regnase-1 expression through the destabilization of its transcript. Overall, our study identifies protein interactors of endogenously expressed Regnase factors, characterizes the regulatory interplay between Regnase family members in mast cells, and establishes their role in the control of mast cell homeostasis and inflammatory responses.
(© 2024 Bataclan et al.)
Databáze: MEDLINE