Title : Profiling of human IL-22+ T cell clones from patients affected with schistosoma mansoni: Insights into macrophage regulation and liver fibrosis
Abstract:
Tissue damage caused by Schistosoma mansoni infection is primarily due to a granulomatous, T-cell-mediated response to eggs, which ultimately leads to liver fibrosis and portal hypertension. In the early phase of infection, the immune response is dominated by Th1 lymphocytes; however, over time, there is a downregulation of Th1 cytokines and a predominant Th2 response against egg antigens. This shift contributes to hepatic stellate cell activation, extracellular matrix deposition, and subsequent liver fibrosis. Despite significant advances in understanding these processes, the precise nature of the immune response and its regulatory mechanisms remain unclear.
In this study, we analyzed the human T cell response to soluble egg antigen (SEA) and characterized the cytokine profiles of 121 T cell clones (Tcc) derived from the peripheral blood of three patients infected with Schistosoma mansoni. All Tccs produced abundant IL-13 upon anti-CD3 activation, while a limited subset (n=33) release low levels of IFN-γ, and 38 Tccs exhibited variable production of IL-10. Notably, 51 Tccs also produce IL-22 in addition to IL-13.
To explore the potential role of IL-22 in liver granulomatous reaction to Schistosoma mansoni eggs, we assessed in vitro the expression of IL-22 receptor (IL-22R) on both human M0 and M2 macrophages, the latter being the predominant macrophage population known to be involved in parasitic infections. Both cell subsets express IL-22R by flow cytometry and western blot analysis. IL-22R engagement induced phosphorylation of p38, p-STAT3, and p-STAT5. Additionally, IL-22 reduced the expression of M2 markers CD163 and CD200R induced by IL-13 in macrophages.
Furthermore, treatment of hepatic stellate cell with IL-22 significantly inhibited the production of collagen types I and III and proliferation induced by IL-13.
In conclusion, our findings provide evidence that IL-22+ cells regulate Th2 polarization of macrophages during Schistosoma infection and negatively affect liver fibrosis by acting directly on hepatic stellate cells.
