Extracellular CIRP co-stimulated T cells through IL6R/STAT3 in pediatric IgA vasculitis.

Abstract

Immunoglobulin A vasculitis (IgAV) is the most common vasculitis of childhood. Disordered immune responses play important roles in its pathogenesis, but the comprehensive immune profile of the disease and the underlying mechanisms are still largely unknown. Here we found a potential disease biomarker cold inducible RNA binding protein (CIRP) in our pediatric IgAV cohort. Serum CIRP level in these patients were elevated and positively correlated with the increased early memory (CD45RA+CD62L+CD95+) T cells revealed using multicolor flow cytometry. Immune phenotyping of the patients showed they had more activated T cells with higher IL6Ra expression. T cell culture experiment showed CIRP further activated both human CD4+ and CD8+ T cells as indicated by increased perforin secretion and phosphorylation of STAT3. Blockade of IL6Rα attenuated CIRP-induced T cell toxicity in vitro. RNA-sequencing data further supported CIRP stimulation promoted human T cell activation and migration, fueled inflammation through the JAK-STAT signaling pathway. Therefore, IL6Ra-mediated T cell activation by extracellular CIRP may contribute to pathogenesis of IgAV in children, both CIRP and IL6Ra could be new therapeutic targets for IgAV.

• Authors: Hong Lei, Dan Li, Mingyue Duan, Yuanyuan Zhang, Ying Sun, Jun She, Xi Zhang, Petra Reinke, Hans-Dieter Volk, Yanmin Zhang, Yi Lv, Rongqian Wu
• Journal: Biochimica et biophysica acta. Molecular basis of disease (Biochim Biophys Acta Mol Basis Dis) Vol. 1870 Issue 5 Pg. 167151 (Apr 01 2024) ISSN: 1879-260X [Electronic] Netherlands
• PMID: 38565387 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier B.V. All rights reserved.