{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:39:44Z","timestamp":1792795184379,"version":"4.5.0"},"reference-count":36,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:p>Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL\/6 mice (H-2<jats:sup>b<\/jats:sup>) were orthotopically transplanted to nephrotomized BALB\/c mice (H-2<jats:sup>d<\/jats:sup>). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup>Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and\/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.<\/jats:p>","DOI":"10.1152\/ajprenal.00258.2011","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T00:28:37Z","timestamp":1319675317000},"page":"F276-F283","source":"Crossref","is-referenced-by-count":18,"title":["Prolonged renal allograft survival by donor interleukin-6 deficiency: association with decreased alloantibodies and increased intragraft T regulatory cells"],"prefix":"10.1152","volume":"302","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery, The University of Western Ontario, London, Ontario;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiunong","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia;"},{"name":"Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Western Ontario, London, Ontario;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia;"},{"name":"Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Western Ontario, London, Ontario;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher Y. 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