Extracellular CIRP co-stimulated T cells through IL6R/STAT3 in pediatric IgA vasculitis.
Biochim Biophys Acta Mol Basis Dis
; 1870(5): 167151, 2024 06.
Article
en En
| MEDLINE
| ID: mdl-38565387
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
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Proteínas de Unión al ARN
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Receptores de Interleucina-6
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Factor de Transcripción STAT3
Límite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos