IL-17A-producing ?? T cells promote liver pathology in acute murine schistosomiasis.

ABSTRACT:

Background

The main symptoms of schistosomiasis are granuloma and fibrosis, caused by Schistosoma eggs. Numerous types of cells and cytokines are involved in the progression of Schistosoma infection. As a class of innate immune cells, ?? T cells play critical roles in the early immune response. However, their role in modulating granuloma and fibrosis remains to be clarified.

Methods

Liver fibrosis in wild-type (WT) mice and T cell receptor (TCR) ? knockout (KO) mice infected with Schistosoma japonicum was examined via Masson's trichrome staining of collagen deposition and quantitative reverse transcriptase-PCR (RT-PCR) of fibrosis-related genes. Granuloma was detected by hematoxylin-eosin (H&E) staining and quantified. Flow cytometry was used for immune cell profiling and for detecting cytokine secretion. The abundance of the related cytokines was measured using quantitative RT-PCR.

Results

The livers of S. japonicum-infected mice had significantly increased proportions of interleukin (IL)-17A producing ?? T cells and secreted IL-17A. Compared with the WT mice, TCR ? deficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of ?? T cells in infected mice were associated with enhanced CD11b⁺Gr-1⁺ cells, concurrent with increased expression of transforming growth factor (TGF)-? in the liver.

Conclusions

In this mouse model of Schistosoma infection, ?? T cells may promote liver fibrosis by recruiting CD11b⁺Gr-1⁺ cells. These findings shed new light on the pathogenesis of liver pathology in murine schistosomiasis.

SUBMITTER: Sun L 

PROVIDER: S-EPMC7329544 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature