Both Th2 and Th17 responses are involved in the pathogenesis of Churg-Strauss syndrome

Clinical and Experimental Rheumatology

Barbara Sokolowska¹  Andrzej Szczeklik¹  Bogdan Jakiela¹  Wojciech Szczeklik¹  Lucyna Mastalerz¹  Marek Sanak¹  Hanna Plutecka¹  Jacek Musial¹ 

关键词: Churg-Strauss syndrome;    T helper cells;    Th2 cells;    Th17 cells;    CCR4-active chemokines;    Immunosuppressive treatment;    Churg-Strauss syndrome;   

DOI  :  

学科分类：医学（综合）

来源: Pacini Editore SpA

【 摘 要 】

OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare systemic vasculitis associated with eosinophilia and granuloma formation. The contribution of individual T-helper cell lineages in pathogenesis of CSS is unknown. We hypothesised that in CSS an imbalance of major effector T-cell subpopulations takes place, and is further influenced by the mode of treatment. METHODS: We investigated the immunophenotype, cytokine production and transcriptome profile in peripheral blood lymphocytes (PBL) from 19 patients with stable CSS (10 were treated with glucocorticoids alone (CSS/GC), 9 with steroids and other immunosuppressive drugs (CSS/IS)), and 13 healthy controls. Furthermore, serum IL-5 and CCR4-active chemokines (CCL17, CCL22) were measured in six patients with active disease and upon remission. RESULTS: All CSS patients had decreased percentage of FoxP3+ regulatory T cells. In the CSS/GC group we found an increase in the Th17/Treg ratio and up-regulation of both Th2 and Th17 markers as evidenced by (1) over expression of Th2-related genes (GATA3, STAT6) in PBL, (2) elevated concentrations of serum IL-5 and CCL17, and (3) a concomitant increase in the number of Th17 cells, and secretion of IL-17A by stimulated PBL. The level of CCR4-active chemokines was increased in active-CSS, and correlated with blood eosinophilia. The combined treatment with steroids and other immunosuppressive drugs was associated with a significant decrease in both Th2-related chemokines and the number of Th17 cells. CONCLUSIONS: Our results indicate that both Th2 and Th17 lineages are involved in the pathogenesis of CSS, while CCR4-active chemokines contribute to eosinophilia in the active disease. These phenomena are down regulated by immunosuppressive therapy.

【 授权许可】

Unknown