アクティブボード・2007年 2月
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研究発表を行った学会; 第36回日本免疫学会総会・学術集会
   2006年12月11日〜13日(大阪)
タイトル; G5PR is indispensable for differentiation and survival of T lineage cells.
発表者; Xing Yan 氏
   (熊本大学 大学院医学薬学研究部 免疫学分野)
Abstract;
Our previous study has shown that a loss of G5PR increased the susceptibility to BCR-mediated apoptosis associated with an increased depolarization of the mitochondrial membrane and the enhanced activation of JNK and Bim. Here we found that G5PR is expressed strongly in T lineage cells, and studied the function of G5PR in T lymphocyte. We generated T cell-specific G5PR conditional knockout (G5PR-T-KO) mice by crossing the floxed-G5pr mice with Lck-cre transgenic mice. G5PR-T-KO mice revealed thymic atrophy with marked reduction of total thymocytes (~8-fold). Flow cytometric analysis of thymocytes demonstrated the reduction of double positive (DP) cells as 10% of control mice and few single positive (SP) cells. However, double negative (DN) cells are maintained equivalent level, suggesting that G5PR is required for differentiation from DN cells to DP cells or their survival. In the culture of thymocytes in vitro, after 24 hours nearly 80% of the G5PR-deficient thymocytes underwent spontaneous apoptosis, on the other hand, half of control thymocytes survived in culture medium. TUNEL analysis demonstrated the increase of apoptosis of the cells within cortical regions where the DN cells develop into DP cells. We studied the various kinase activity as a target in G5PR-deficient thymocytes and found a hyper-phosphorylation of JNK and p38 MAP kinase. G5PR plays a crucial role for early thymocyte development and survival presumably by regulating JNK and p38 kinase activity.