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《Current Immunology》 2011-01
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Tryptophan metabolism through indoleamine 2,3-dioxygenase/tryptophanyl t-RNA sythetase metabolic pathway effects proliferation of synovial autoreactive T cells in rheumatoid arthritis

JIN Min,ZHU Ling-qiao,ZHANG Yan-yun(Shanghai Institute of Immunology,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)  
A hallmark of T cell-mediated autoimmunity is the persistence of the autoreactive T cells.We have found that dendritic cells(DC) and tissues from the synovial joints of RA patients expressed higher levels of indoleamine 2,3-dioxygenase(IDO) than DC from healthy donors.Interestingly,T cells derived from the joint synovial fluid(SF) of RA patients proliferated in response to either autologous or allogeneic IDO-positive DCs,which was not affected by the addition of IDO inhibitor 1-methyl-D-tryptophan(1-MT).In contrast,addition of 1-MT to the culture stimulated with allogeneic or autologous IDO-positive DCs significantly enhanced the proliferation of T cells derived from peripheral blood of healthy donors or from PB of RA patients.Furthermore,we found that functionally active tryptophanyl-tRNA-synthetase(TTS) was significantly elevated in T cells derived from the SF of RA patients,leading to enhanced storage of tryptophan in T cells and the subsequent resistance to IDO-mediated deprivation of tryptophan.Specifically blocking of the up-regulation of TTS expression in T cells presents an avenue for development of a novel therapeutic approach for the treatment of RA.
【Fund】: 国家自然科学基金资助项目(NSF30873045);; 上海市基础研究重点资助项目(08JC1413300)
【CateGory Index】: R593.22
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