HMGB1 is an early and critical mediator in an animal model of uveitis induced by IRBP‐specific T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: autoimmune disease;    experimental autoimmune uveitis;    immunoregulation;    autoreactive T cells;    damage‐;    associated molecular patterns;    pathogen recognition receptors;   

DOI  :  10.1189/jlb.0613337

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ItislargelyunknownhowinvadingautoreactiveTcellsinitiatethepathogenicprocessinsidethediseasedorganinorgan‐specificautoimmunedisease.Inthisstudy,weusedachronicuveitisdiseasemodelinmice—EAU—inducedbyadoptivetransferofuveitogenicIRBP‐specificTcellsandshowedthatHMGB1,animportantendogenousmoleculethatservesasadangersignal,wasreleasedrapidlyfromretinalcellsintotheECMandintraocularfluidinresponsetoIRBP‐specificTcelltransfer.HMGB1releaserequireddirectcell–cellcontactbetweenretinalcellsandIRBP‐specificTcellsandwasanactivesecretionfromintactretinalcells.AdministrationofHMGB1antagonistsinhibitedseverityofEAUsignificantlyviamechanismsthatincludeinhibitionofIRBP‐specificTcellproliferationandtheirIFN‐γandIL‐17production.TheinflammatoryeffectsofHMGB1maysignaltheTLR/MyD88pathway,asMyD88−/−micehadahighlevelofHMGB1intheeyebutdidnotdevelopEAUafterIRBP‐specificTcelltransfer.OurstudydemonstratesthatHMGB1isanearlyandcriticalmediatorofocularinflammationinitiatedbyautoreactiveTcellinvasion...

【 授权许可】

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