Reg3g overexpression promotes β cell regeneration and induces immune tolerance in nonobese‐diabetic mouse model

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

关键词: regulatory T cell;    dendritic cell;    type 1 diabetes;   

DOI  :  10.1189/jlb.3A0815-371RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theregeneratingislet‐derivedgenewasfirstisolatedinregeneratedpancreastissues,greatlycontributingtoβcellregeneration.Itisananti‐inflammatoryinresponsetocellularstress.ThisencouragedustoinvestigatetheexactroleofanovelmemberofRegfamily,regeneratingislet‐derivedgeneγ,intype1diabetesofnonobese‐diabeticmice.Forthis,Reg3ggenewasoverexpressedinpancreaticislets,andconferredbeneficialeffectsonβcellregenerationthroughactivatingtheJanuskinase2/signaltransducerandactivatoroftranscription3/nuclearfactorκBsignalingpathway.Lentiviralvector‐encodingregeneratingislet‐derivedgeneγtreatmentalsodecreasedlymphocyteinfiltratesoftheintra‐isletandperi‐isletbyinducingbothdifferentiationofregulatoryTcellandimmaturedendriticcellsoftolerogenicproperties,whichattenuatedautoimmunity.Thistreatmentfurthercontributedtorebalancedlevelsoftype1/2helperTcellcytokinesandelevatedα1‐antitrypsinlevelsintheserum.Theseresultswerenotobservedinphosphate‐bufferedsaline‐treatedmiceorinlentivirus‐controlmice.Wehaveshown,forthefirsttime,toourknowledge,thatregeneratingislet‐derivedgeneγpromotesβcellregenerationandpreservesβcellsfromautoimmunitydamagebyincreasingregulatoryTcelldifferentiationandinducingtolerateddendriticcells.Thisregeneratingislet‐derivedgeneγinfusioncouldprobablybedevelopedintoanoptimalgenetherapyforthepreventionandreversaloftype1diabetes...

【 授权许可】

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