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

[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...

[学科分类] 生理学

[关键词] TGF‐βIL‐10;IL‐2;IFN‐γCCL2;CXCL12