Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis
Background: Tonsillitis can promote the progression of IgA nephropathy (IgAN) by aggravating immunopathologic response. Th22 cell disorder is involved in the pathogenesis of IgAN with tonsillitis. This study was determined to explore the possible mechanism of IgAN with tonsillitis underlying Th22 cell chemotaxis response to the effect of CCL20, CCL22, and CCL27. Methods: This research was conducted on 65 subjects including 16 healthy controls (HC group), 5 patients with renal carcinoma (HTC group) and 44 patients with IgAN between 2015 and 2016. According to clinical symptoms and results of throat swab culture, patients with IgAN were divided into two groups: IgAN with tonsillitis (IgAN + tonsillitis, n = 14) and IgAN patients without tonsillitis (IgAN, n = 30). Distribution of Th22 cells in IgAN patients was determined. The expression of CCL20, CCL22, and CCL27 in both peripheral blood and kidneys of IgAN patients was investigated. Severity of pathological lesions in IgAN patients was analyzed. Coculture assay and transwell assay were performed to explore the impacts of human mesangial cells (HMC) on Th22 cell chemotaxis and Th22 cell local accumulation under hemolytic streptococcus (HS) infection. Results: Th22 cell percentages in IgAN patients increased compared with healthy controls. This increased Th22 cell percentage was positively correlated with the renal lesions of IgAN patients. Correspondingly, the expression of CCL20, CCL22, and CCL27 in renal tissue increased in IgAN patients. Tonsillitis exacerbated these overrepresentations of Th22 cells and chemokines. It was found that HMC could produce CCL20, CCL22, and CCL27. The supernatant of HMC was chemotactic for Th22 cells. This activity of HMC was stimulated by HS infection, whereas treatment of anti-CCL20, anti-CCL22, and anti-CCL27 antibodies partly blocked this chemoattractant effect of HMC. Conclusions: Tonsil infection may aggravate the renal pathological lesions of IgAN by exacerbating Th22 cell accumulation. Our data suggested a collaboration between HMC and Th22 cells in IgAN with tonsillitis underlying the effects of CCL20, CCL22, and CCL27.Keywords: CCL20; CCL22; CCL27; IgA Nephropathy; Th22 Cells; Tonsillitis.
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基因水平:PCR Array、RT-PCR、PCR、单细胞测序
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细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
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