Dominant trait linked to chromosome 1 in DBA/2 mice for the resistance to autoimmune gastritis appears in bone marrow cells.
Dominant trait linked to chromosome 1 in DBA/2 mice for the resistance to autoimmune gastritis appears in bone marrow cells.
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DOI：
10.1538/expanim.63.155
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发表时间：
2014
影响因子：
2.4
通讯作者：
Hosono M
中科院分区：
文献类型：
--
作者：
Fujii M;Suzuki K;Suenaga S;Wakatsuki M;Kushida Y;Touma M;Hosono M
新生儿胸腺切除术（NTx）在BALB/c小鼠（人类A型慢性萎缩性胃炎的模型）中诱导自身免疫性胃炎（AIG），但在DBA/2小鼠中不诱导，在CDF 1小鼠（BALB/c和DBA/2小鼠的杂交种）中也很少诱导。本研究旨在阐明DBA/2显性遗传小鼠抗AIG的机制。用CDF 1-BALB/c回交检测与AIG抗性相关的连锁群和与AIG抗性相关的细胞。对接受DBA/2-骨髓细胞的NTx BALB/c小鼠和NTx DBA/2-嵌合BALB/c小鼠进行细胞内染色和流式细胞术珠阵列检测几种细胞因子。在NTx BALB/c小鼠中，分泌IFN-γ的CD 4 + T细胞增加，但在NTx DBA/2小鼠中不增加。由于携带Vβ6+ T细胞的小鼠中有一半发生了AIG，而另一半Vβ6+ T细胞阴性的小鼠几乎没有发生，因此对AIG产生的抗性与DBA/2小鼠1号染色体上Mls-1a基因座的存在有关，该基因座删除了Vβ6+ T细胞。NTx DBA/2嵌合体BALB/c小鼠表现出优势的IL-10产生和对AIG的抗性，尽管从Mls-1a位点分离实验发现Vβ6+ T细胞的缺失不是AIG抗性的原因。虽然NTx DBA/2嵌合BALB/c小鼠没有患AIG，但它们带来了AIG的T细胞的直接前体。可以得出结论，DBA/2小鼠产生产生抗炎细胞因子以防止AIG-T细胞活化的骨髓源性细胞。
Neonatal thymectomy (NTx) induces autoimmune gastritis (AIG) in BALB/c mice, a model for human type A chronic atrophic gastritis, but not in DBA/2 mice and rarely in CDF1 mice (a hybrid of BALB/c and DBA/2 mice). The aim of this study was to clarify the mechanisms of AIG-resistance in mice bearing the dominant trait of DBA/2. Linkage groups associated with, and cells related to AIG resistance were examined with CDF1-BALB/c backcrosses. Intracellular staining and flow-cytometric bead array for several cytokines were performed on NTx BALB/c mice and NTx DBA/2-chimeric BALB/c mice receiving DBA/2-bone marrow cells. In NTx BALB/c mice, IFN-γ-secreting CD4+ T cells were increased, but not in NTx DBA/2 mice. Because Vβ6+ T cell-bearing mice of half of their backcrosses developed AIG, but the other half of Vβ6+ T cell-negative mice developed scarcely, resistance for AIG generation is associated with the presence of the Mls-1a locus on chromosome 1 in DBA/2 mice, which deletes Vβ6+ T cells. NTx DBA/2-chimera BALB/c mice showed dominant production of IL-10 and resistance for AIG, although the deletion of Vβ6+ T cells was found not to be a cause of AIG-resistance from Mls-1a locus segregation experiments. Although NTx DBA/2-chimeric BALB/c mice did not suffer from AIG, they brought immediate precursors of T cells for AIG. It is concluded that DBA/2 mice generate bone marrow-derived cells that produce anti-inflammatory cytokines to prevent the activation of AIG-T cells.