{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:01:41Z","timestamp":1785265301854,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013132","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","award":["J86C18001110005"],"award-info":[{"award-number":["J86C18001110005"]}],"id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNR (National Research Council)-CNCCS","award":["DSB.AD10.061 and DSB.AD010.051"],"award-info":[{"award-number":["DSB.AD10.061 and DSB.AD010.051"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Tissue damage in <jats:italic>Schistosoma mansoni<\/jats:italic> infection results from a granulomatous, T cell\u2013mediated 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 <jats:italic>S. mansoni<\/jats:italic>\u2013infected patients. All clones produced high levels of IL-13 upon anti-CD3 stimulation; a minority secreted IFN-\u03b3 (n\u2009=\u200933) or IL-10 (n\u2009=\u200938). Notably, 51 clones co-produced IL-22 and IL-13. To investigate IL-22\u2019s 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\u2013induced M2 markers (CD163, CD200R). Furthermore, IL-22 treatment of HSCs inhibited IL-13\u2013driven collagen I\/III production and cell proliferation. These results suggest that IL-22\u2013producing 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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0013132","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T17:53:57Z","timestamp":1748627637000},"page":"e0013132","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Profiling of human IL-22+ T cell clones from patients affected with Schistosoma mansoni: Insights into macrophage regulation and liver 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