The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications

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

关键词: TGF‐;    β;    IL‐;    10;    IL‐;    2;    IFN‐;    γ;    CCL2;    CXCL12;   

DOI  :  10.1189/jlb.0612293

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Cytokinesandchemokinesaresecreted,smallcell‐signalingproteinmolecules,whosereceptorsareexpressedonimmunecells.Thesefactorsplayacriticalroleinimmunecelldifferentiation,migration,andpolarizationintofunctionalsubtypesandindirectingtheirbiologicalfunctions.Muchattentionhasbeendevotedtoexploringtheroleofkeyinflammatorycytokinesandpromigratorychemokinesinautoimmune,autoinflammatory,andallergicdiseases,leadingtodevelopmentoftherapeuticstrategiesthatarebasedontheirtargetedneutralization.Recentstudies,includingthosecomingfromourgroups,showthatseveralmajorproinflammatorycytokinesandchemokines,includingIFN‐γ,IL‐2,CCL2,andCXCL12,mayalsofunctionasanti‐inflammatorymediatorsandtherefore,mayhavepotentialasanti‐inflammatorydrugs.Likewise,majoranti‐inflammatorymediators,suchasTGF‐β,mayundercertainconditions,incombinationwithothercytokines,exhibitproinflammatoryfunctionanddirectthepolarizationofthehighlyinflammatoryCD4+Th17cells.Weshowherethatthebiologicalfunctionofpro‐andanti‐inflammatorycytokinesisdependentonthreekeyparameters:thelocalconcentrationofagivencytokine,thestageofdiseaseinwhichitisadministered,anditscombinationwithothercytokines.Thetherapeuticimplicationsofthesefindingsarediscussed,includingtwoveryrecentstudiessummarizingclinicaltrials,inwhichlow‐doseadministrationofIL‐2wasusedtosuccessfullysuppressHCVandGVHD...

【 授权许可】

CC BY