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α-Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation
Gong Y.1; Zhang R.1; Zhang J.1; Xu L.1; Zhang F.1; Xu W.1; Wang Y.1; Chu Y.1; Xiong S.2
2008-05-01
Source PublicationFASEB Journal
ISSN08926638
Volume22Issue:5Pages:1426-1439
Abstractα-Dystroglycan has been proved to be involved in lymphocyte activation by participating in immunological synapse (IS) formation. Considering the existence of IS formation in thymic development, we questioned whether α-dystroglycan was expressed in thymus and influenced thymic development. In this study, we demonstrated that α-dystroglycan was expressed on fetal thymocytes, especially on double-positive (DP, CD4CD8) cells. Blocking α-dystroglycan by treatment of fetal thymus organ culture (FTOC) with anti-α-dystroglycan antibody IIH6C4 decreased the number of DP cells compared with nontreated or isotype antibody controls. Down-regulation of α-dystroglycan by retroviruses carrying antisense cDNA of dystroglycan in reaggregate thymus organ culture (RTOC) further confirmed these results. Enhanced apoptosis of DP cells was observed after blocking α-dystroglycan. Interestingly, we found that blocking α-dystroglycan reduced IS formation between DP cells and thymic epithelial cells. Furthermore, blocking α-dystroglycan up-regulated CD95/CD95L expression and reduced Bcl-2 expression on DP cells in the developing thymus. Finally, the increase in the apoptosis of DP cells was associated with a consequent decrease in the positive selection, as indicated by the reduction of both ERK phosphorylation in DP cells and single-positive (SP, CD4 or CD8) cell outcome. Altogether, these results indicated that α-dystroglycan was involved in positive selection of thymocytes by participating in the IS formation. © FASEB.
KeywordFetal thymus organ culture Reaggregate thymus organ culture Thymic development
DOI10.1096/fj.07-9264com
URLView the original
Language英語
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被引频次[WOS]:2   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题University of Macau
Affiliation1.Fudan University Shanghai Medical College
2.E-Institutes of Shanghai Universities
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Gong Y.,Zhang R.,Zhang J.,et al. α-Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation[J]. FASEB Journal,2008,22(5):1426-1439.
APA Gong Y..,Zhang R..,Zhang J..,Xu L..,Zhang F..,...&Xiong S..(2008).α-Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation.FASEB Journal,22(5),1426-1439.
MLA Gong Y.,et al."α-Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation".FASEB Journal 22.5(2008):1426-1439.
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