Involvement of the CX3CL1 (fractalkine)/CX3CR1 pathway in the pathogenesis of acute graft‐versus‐host disease

[摘要] ThisstudyinvestigatedtheroleofcytokinesandchemokinesinaGVHDincidenceandseverityin109patientswhounderwentreduced‐intensityconditioningallogeneicstemcelltransplantation(HSCT).Amongthe42cytokinestestedatd0HSCT,onlyCX3CL1levelsatd0HSCTweresignificantlyassociatedwithGradesII–IVaGVHDdevelopment(P=0.04).IncreasedlevelsofCX3CL1atd20–30and50post‐HSCTwerealsosignificantlyassociatedwithaGVHD(P=0.02andP=0.03,respectively).Nosuchassociationwasfoundbeforetheconditioningregimenoratd100–120post‐HSCT.AsthereceptorforCX3CL1isCX3CR1,thenumberofCX3CR1+cellswasdeterminedbyflowcytometry.TheCX3CR1+CD8+TcellproportionwassignificantlyhigherinpatientswithaGVHDthanthosewithoutaGVHD(P=0.01).ToinvestigatethedistributionoftheCX3CL1/CX3CR1axisintheanatomicsitesofaGVHD,CX3CL1andCX3CR1levelswerestudiedbyuseofaninsituimmunohistochemicalanalysisonGIbiopsiesofpatientswithintestinalaGVHD.CX3CL1expressionwasincreasedsignificantlyintheepithelialcellsandmononuclearcellsofthelaminapropria.CX3CR1+mononuclearcellswereidentifiedinclosecontactwithepithelialcells.ThesefindingsstronglysuggesttheimplicationoftheCX3CL1/CX3CR1axisinthepathogenesisofaGVHD...

[学科分类] 生理学

[关键词] allogeneic transplant;stem cell;alloreactivity;endothelium