Tissue damage in Schistosoma mansoni infection results from a granulomatous, T cell-mediated response to parasite eggs, leading to liver fibrosis and portal hypertension. This immune response, initially Th1-dominated, progressively shifts toward a Th2 profile, contributing to hepatic stellate cell (HSC) activation and fibrosis. However, the precise regulatory mechanisms remain unclear. In this study, we analyzed T cell responses to soluble egg antigens (SEA) in 121 T cell clones (Tcc) from S. mansoni-infected patients. All clones produced high levels of IL-13 upon anti-CD3 stimulation; a minority secreted IFN-γ (n = 33) or IL-10 (n = 38). Notably, 51 clones co-produced IL-22 and IL-13. To investigate IL-22's role, we examined IL-22 receptor (IL-22R) expression on human M0 and M2 macrophages. Both subsets expressed IL-22R, and its engagement triggered phosphorylation of p38, STAT3, and STAT5. IL-22 also downregulated IL-13-induced M2 markers (CD163, CD200R). Furthermore, IL-22 treatment of HSCs inhibited IL-13-driven collagen I/III production and cell proliferation. These results suggest that IL-22-producing T cells modulate Th2 macrophage polarization and directly suppress fibrogenesis in HSCs. IL-22 may thus act as a regulatory cytokine counteracting liver fibrosis during schistosomiasis.
Copyright: © 2025 Scopelliti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.