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α‐Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation
Author(s) -
Gong Yanping,
Zhang Ruihua,
Zhang Jinping,
Xu Lin,
Zhang Feng,
Xu Wei,
Wang Ying,
Chu Yiwei,
Xiong Sidong
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-9264com
Subject(s) - dystroglycan , microbiology and biotechnology , cd8 , biology , alpha (finance) , immunological synapse , t cell , immunology , t cell receptor , immune system , laminin , medicine , extracellular matrix , construct validity , nursing , patient satisfaction
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 doublepositive (DP, CD4 + CD8 + ) cells. Blocking α‐dystrogly‐ can 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‐dystro‐ glycan by retroviruses carrying antisense cDNA of dys‐ troglycan 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.—Gong, Y., Zhang, R., Zhang, J., Xu, L., Zhang, F., Xu, W., Wang, Y., Chu, Y., Xiong, S. α‐Dystroglycan is involved in positive selection of thymocytes by participating in immunological synapse formation. FASEB J . 22, 1426–1439 (2008)