Functional overlap but differential expression of CSF‐1 and IL‐34 in their CSF‐1 receptor‐mediated regulation of myeloid cells

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

关键词: macrophages;    osteoclasts;    cytokines;    hematopoiesis;    inflammation;    tumor‐;    associated macrophages;   

DOI  :  10.1189/jlb.1209822

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CSF‐1isbroadlyexpressedandregulatesmacrophageandosteoclastdevelopment.TheactionandexpressionofIL‐34,anovelCSF‐1Rligand,wereinvestigatedinthemouse.Asexpected,huIL‐34stimulatedmacrophageproliferationviathehuCSF‐1R,equivalentlytohuCSF‐1,butwasmuchlessactiveatstimulatingmousemacrophageproliferationthanhuCSF‐1.LikemuCSF‐1,muIL‐34andamuIL‐34isoformlackingQ81stimulatedmousemacrophageproliferation,CSF‐1Rtyrosinephosphorylation,andsignalingandsynergizedwithothercytokinestogeneratemacrophagesandosteoclastsfromculturedprogenitors.However,theyrespectivelypossessedtwofoldandfivefoldloweraffinitiesfortheCSF‐1Randcorrespondingly,loweractivitiesthanmuCSF‐1.Furthermore,muIL‐34,whentransgenicallyexpressedinaCSF‐1‐dependentmannerinvivo,rescuedthebone,osteoclast,tissuemacrophage,andfertilitydefectsofCsf1op/opmice,suggestingsimilarregulationofCSF‐1R‐expressingcellsbyIL‐34andCSF‐1.Whole‐mountIL34insituhybridizationandCSF‐1reporterexpressionrevealedthatIL34mRNAwasstronglyexpressedintheembryonicbrainatE11.5,priortotheexpressionofCsf1mRNA.QRT‐PCRrevealedthatcomparedwithCsf1mRNA,IL34mRNAlevelswerelowerinpregnantuterusandinculturedosteoblasts,higherinmostregionsofthebrainandheart,andnotcompensatorilyincreasedinCsf1op/opmousetissues.Thus,thedifferentspatiotemporalexpressionofIL‐34andCSF‐1allowsforcomplementaryactivationoftheCSF‐1Rindevelopingandadulttissues...

【 授权许可】

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