SerpinB1 regulates homeostatic expansion of IL‐17+ γδ and CD4+ Th17 cells

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

关键词: lymphocytes;    population size;    cell proliferation;    inflammation;    cytokine regulation;   

DOI  :  10.1189/jlb.0613331

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

SerpinB1isanendogenousinhibitorofserineproteasesrecognizedforitsanti‐inflammatoryandhost‐protectiveproperties.AlthoughlossofserpinB1inmicedoesnotresultingrossimmunederegulation,serpinb1a−/−micedisplayincreasedmortalityandinflammation‐associatedmorbidityuponchallengewithinfluenzavirus.Here,weshowthatIL‐17A+γδandCD4+Th17cellsarealreadyexpandedinthelungsofserpinb1a−/−miceatsteady‐state.Bothγδandαβ+CD4+CCR6+Tcellsisolatedfromthelungsofnaiveserpinb1a−/−micedisplayedaskewedtranscriptionalprofilerelativetoWTcells,includingincreasedTh17signaturetranscripts[Il17a,l17f,andRorc(RORγt)]anddecreasedTh1signaturetranscripts[Ifng,Cxcr3,andTbx21(T‐bet)]inγδTcells.Inadditiontothelung,IL‐17A+γδandCD4+Th17cellswereincreasedinthespleenofnaiveserpinb1a−/−mice,despitenormalαβandγδTcelldevelopmentinthethymus.WithintheγδTcellcompartment,lossofserpinb1apromptedselectiveexpansionofVγ4+andVγ6/Vδ1+cells,whichalsodisplayedelevatedexpressionoftheproliferatingcellnuclearantigen,Ki‐67,andIL‐17A.Giventhatserpinb1aispreferentiallyexpressedinWTIL‐17A+γδandCD4+Th17cellsubsetsvis‐à‐visotherTcelllineages,ourfindingsrevealanovelfunctionofserpinB1inlimitinguntowardexpansionoflymphocyteswithaTh17phenotype...

【 授权许可】

CC BY