Hemolytic streptococcus exacerbates tubulointerstitial lesions in IgA nephropathy through Th22 cells chemotaxis and proliferation.

BACKGROUND

Tonsillitis and the immunopathologic response induced by it are essential for IgA nephropathy (IgAN) progression. In this study, we investigated the possible mechanism underlying Th22 cells overrepresentation in tonsillitis related IgAN.

METHODS

The distribution of Th22 cells, and the expressions of CCR10 and CCL27 in IgAN patients were detected. Relationship between Th22 cell chemotaxis and renal pathology lesions was determined. Transwell assay was performed to investigate the contribution of human tubular epithelial cell (human kidney 2 cell, HK2) to Th22 cell chemokines underlying Hemolytic streptococcus (HS) infection. Additionally, the impacts of tubular inflammatory on Th22 cell proliferation were investigated.

RESULTS

Th22 cells were significantly increased in IgAN patients. Accordingly, the expressions of CCR10 and CCL27 were increased in IgAN patients. Higher Th22 cells, CCR10 and CCL27 correlated with severer tubulointerstitial lesions. It was observed that CCR10 and CCL27 were predominantly expressed on tubular epithelial cells, and supernatants of HK2 were chemotactic for Th22 cells. This activity of HK2 was partly blocked by anti-CCL27. Tonsillitis promoted the over expression of Th22 cells, CCR10 and CCL27 in IgAN patients, and exacerbated their renal lesions. Inactivated HS aggravated Th22 cell chemotaxis by promoting CCL27 secretion. Additionally, inactivated HS could accelerate Th22 cell proliferation by promoting the secretion of IL-1, IL-6 and TNF-α.

CONCLUSION

Th22 cell chemotaxis was involved in the pathogenesis of IgAN. Tubular epithelial cells are vulnerable to Th22 cell chemotaxis in IgAN. Tonsillitis may exacerbate the progression of IgAN by promoting Th22 cell chemotaxis and cell proliferation.