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

[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...

[学科分类] 生理学

[关键词] lymphocytes;population size;cell proliferation;inflammation;cytokine regulation