IL-17A-producing γδ T cells promote liver pathology in acute murine schistosomiasis
IL-17A-producing γδ T cells promote liver pathology in acute murine schistosomiasis
复制标题
产生 IL-17A 的 γT 细胞促进急性小鼠血吸虫病的肝脏病理学
DOI：
10.1186/s13071-020-04200-4
复制
发表时间：
2020-07-01
影响因子：
3.2
通讯作者：
Cao, Jianping
中科院分区：
文献类型：
--
作者：
Sun, Lei;Gong, Wenci;Cao, Jianping
背景：血吸虫病的主要症状是由血吸虫卵引起的肉芽肿和纤维化。许多类型的细胞和细胞因子参与血吸虫感染的进展。作为一类先天性免疫细胞，γ δ T细胞在早期免疫应答中发挥关键作用。方法：采用Masson三色染色胶原沉积和逆转录聚合酶链反应（RT-PCR）检测日本血吸虫感染的野生型（WT）小鼠和T细胞受体（TCR）δ基因敲除（KO）小鼠肝纤维化。通过苏木精-伊红（H&E）染色检测肉芽肿并定量。流式细胞术用于免疫细胞分析和检测细胞因子分泌。采用定量RT-PCR方法检测肝组织中相关细胞因子的含量。日本血吸虫感染的小鼠具有显著增加的产生白细胞介素（IL）-17 A的γ δ T细胞和分泌IL-17 A的比例。与WT小鼠相比，TCR δ缺陷导致肝脏病理损伤和纤维化减少，并增加感染小鼠的存活率。结论：在血吸虫感染小鼠模型中，γ δ T细胞通过募集CD 11b（+）Gr-1（+）细胞促进肝纤维化。这些发现为小鼠血吸虫病肝脏病理的发病机制提供了新的线索。
Background: The main symptoms of schistosomiasis are granuloma and fibrosis, caused bySchistosomaeggs. Numerous types of cells and cytokines are involved in the progression ofSchistosomainfection. As a class of innate immune cells, gamma delta 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) delta knockout (KO) mice infected withSchistosoma japonicumwas 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 ofS. japonicum-infected mice had significantly increased proportions of interleukin (IL)-17A producing gamma delta T cells and secreted IL-17A. Compared with the WT mice, TCR delta deficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of gamma delta T cells in infected mice were associated with enhanced CD11b(+)Gr-1(+) cells, concurrent with increased expression of transforming growth factor (TGF)-beta in the liver.Conclusions: In this mouse model ofSchistosomainfection, gamma delta 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.