Abstract

BackgroundThe exacerbation of IgA nephropathy (IgAN) is related to respiratory tract infection with hemolytic streptococcus (HS), but the mechanism is unknown. In this study we investigated the role of chemokine ligand 20 (CCL20) in response to the effect of T helper 17 (Th17) cells in the pathogenesis of IgAN associated with HS.MethodsThirty mice were randomly divided into five groups: control mice (control), IgAN mice (IgAN), HS-infected IgAN mice (HS-IgAN), CCL20-treated IgAN mice (CCL20-IgAN), and CCL20-treated HS infected IgAN mice (CCL20-HS-IgAN). IgAN mice were induced with lipopolysaccharide, carbon tetrachloride and bovine serum albumin. Then the mice were sensitized with CCL20 antibody and infected with alpha-hemolytic streptococcus (α-HS) isolated from tonsils in sequence. Urine Albumin-Creatinine ratio and sediments were measured. The pathological changes in kidney and lung tissues were observed under microscopy. Th17 cells and regulatory T cells (Tregs) in kidneys were tested by flow cytometry. CCL20, IL-17A, IL-6 and IL-21 in the kidneys were detected by ELISA.ResultsThe IgAN mice had albuminuria and microscopic hematuria, renal mesangial proliferation, IgA deposition, high electron dense deposition in glomerular mesangial region, decreased frequency of Tregs, increased frequency of Th17 and Th17-Treg ratio. Furthermore, Th17-related cytokines CCL20, IL-17A, IL-6 and IL-21 were all increased in the kidneys of IgAN mice. Compared with IgAN mice, the manifestations in HS-IgAN mice were more severe, but alleviated in CCL20-treated groups.Conclusionα-HS may exacerbate kidney damage in IgAN through CCL20 response to the effect of Th17 cells.

Highlights

  • IgA nephropathy (IgAN) is the most common primary glomerulonephritis throughout the world, and is more common in younger adults

  • We found that the albumin-to-creatinine ratio (ACR) was significantly elevated in IgAN mice compared with controls (427.90628.43 mg/g vs 66.5767.99 mg/ g, P,0.05)

  • Our data suggest that hemolytic streptococcus (HS) significantly increases and CCL20 antibody significantly decreases ACR in IgAN mice

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Summary

Introduction

IgA nephropathy (IgAN) is the most common primary glomerulonephritis throughout the world, and is more common in younger adults. IgAN is always exacerbated after an upper respiratory tract infection with hemolytic streptococcus (HS), with a-HS being a common type [3]. CD4+ T-helper cells are important mediators involved in the development of glomerulonephritis [4]. Th17 cells are a subgroup of T-helper cells producing interleukin 17 (IL-17), which plays role in inflammation and tissue injury. The exacerbation of IgA nephropathy (IgAN) is related to respiratory tract infection with hemolytic streptococcus (HS), but the mechanism is unknown. In this study we investigated the role of chemokine ligand 20 (CCL20) in response to the effect of T helper 17 (Th17) cells in the pathogenesis of IgAN associated with HS

Methods
Results
Conclusion

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