{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:27:23Z","timestamp":1790270843633,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,25]],"date-time":"2013-08-25T00:00:00Z","timestamp":1377388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81070341"],"award-info":[{"award-number":["81070341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81200306"],"award-info":[{"award-number":["81200306"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Nature Science Foundation of Shanghai","award":["09ZR1406000"],"award-info":[{"award-number":["09ZR1406000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Summary<\/jats:title>High\u2010mobility group box 1 (HMGB<\/jats:styled-content>1) proteins are substantially up\u2010regulated in acute and chronic hepatitis. However, the immunopathogenic role of HMGB<\/jats:styled-content>1 in patients with chronic hepatitis B<\/jats:styled-content> (CHB<\/jats:styled-content>) has not been elucidated. In this study, using a cohort of 36 CHB<\/jats:styled-content> patients, we demonstrated a crucial role for HMGB<\/jats:styled-content>1 to modulate balance between regulatory T<\/jats:styled-content> (T<\/jats:styled-content>reg) and T<\/jats:styled-content> helper 17 (Th17) cells via the toll\u2010like receptor (TLR<\/jats:styled-content>)\u20104\u2010interleukin (IL<\/jats:styled-content>)\u20106 pathway. Serum HMGB<\/jats:styled-content>1 levels were dramatically higher in CHB<\/jats:styled-content> patients and increased along with liver injury, inflammation and fibrosis. Notably, HMGB<\/jats:styled-content>1 increased along with decreased T<\/jats:styled-content>reg\/T<\/jats:styled-content>h17 cells ratios in the periphery or intrahepatic microenvironment, which provides a clue for HMGB<\/jats:styled-content>1 to favour T<\/jats:styled-content>h17 responses whereas inhibit T<\/jats:styled-content>reg responses. For in vitro<\/jats:italic> studies, serum pools were constructed with serum from CHB<\/jats:styled-content> patients at an advanced stage, whereas peripheral blood mononuclear cells (PBMC<\/jats:styled-content>) pools were constructed with cells from those at an early stage. CHB<\/jats:styled-content>\u2010serum significantly enhanced retinoic acid\u2010related orphan receptor\u2010\u03b3t (ROR<\/jats:styled-content>\u03b3t), whereas they inhibited forkhead box P<\/jats:styled-content>3 (F<\/jats:styled-content>oxp3) expression in CHB<\/jats:styled-content>\u2010PBMC<\/jats:styled-content>, which could be reversed by blocking of HMGB<\/jats:styled-content>1, TLR<\/jats:styled-content>4, or IL<\/jats:styled-content>\u20106. Besides, recombinant HMGB<\/jats:styled-content>1 (rHMGB<\/jats:styled-content>1) dose\u2010dependently up\u2010regulated ROR<\/jats:styled-content>\u03b3t whereas down\u2010regulated F<\/jats:styled-content>oxp3 expression in CHB\u2010PBMC<\/jats:styled-content>, and meanwhile, rHMGB<\/jats:styled-content>1 enhanced TLR<\/jats:styled-content>4 and IL<\/jats:styled-content>\u20106 expression in CHB\u2010PBMC<\/jats:styled-content>. Moreover, the axis of HMGB<\/jats:styled-content>1\u2013TLR<\/jats:styled-content>4\u2010IL<\/jats:styled-content>\u20106\u2013T<\/jats:styled-content>reg\/T<\/jats:styled-content>h17 required noncontact interactions between CD<\/jats:styled-content>4 and non\u2010CD<\/jats:styled-content>4 cells. In addition, rHMGB<\/jats:styled-content>1 down\u2010regulated anti\u2010inflammatory proteins on CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> cells whereas up\u2010regulated pro\u2010inflammatory cytokines in CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25\u2212<\/jats:sup> cells. In summary, enriched HMGB<\/jats:styled-content>1 in CHB<\/jats:styled-content> patients shifts T<\/jats:styled-content>reg\/T<\/jats:styled-content>h17 balance to T<\/jats:styled-content>h17 dominance via the TLR<\/jats:styled-content>4\u2010IL<\/jats:styled-content>\u20106 pathway, which exacerbates liver injury and inflammation.<\/jats:p>","DOI":"10.1111\/jvh.12152","type":"journal-article","created":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T01:16:41Z","timestamp":1377479801000},"page":"129-140","source":"Crossref","is-referenced-by-count":66,"title":["Enhanced high\u2010mobility group box 1 (HMGB<\/scp>1) modulates regulatory T<\/scp> cells (T<\/scp>reg)\/T<\/scp> helper 17 (T<\/scp>h17) balance via toll\u2010like receptor (TLR<\/scp>)\u20104\u2010interleukin (IL<\/scp>)\u20106 pathway in patients with chronic hepatitis B"],"prefix":"10.1111","volume":"21","author":[{"given":"J.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Tongji Hospital Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.\u2010P.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.\u2010M.","family":"She","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.\u2010Q.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Tongji Hospital Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhongshan Hospital Fudan University Shanghai 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