Intestinal mast cell progenitors require CD49dβ7 (αAβ7 integrin) for tissue-specific homing
Intestinal mast cell progenitors require CD49dβ7 (αAβ7 integrin) for tissue-specific homing
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DOI：
10.1084/jem.194.9.1243
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发表时间：
2001-11-05
影响因子：
15.3
通讯作者：
Austen, KF
中科院分区：
文献类型：
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作者：
Gurish, MF;Tao, H;Austen, KF
肥大细胞 (MC) 在气道过敏性炎症以及蠕虫感染的肠道免疫反应中至关重要。骨髓 (BM) 来源的祖细胞的单一谱系从循环中移出，并在不同组织中成熟为表型不同的 MC。由于 MC 祖细胞 (MCp) 归巢到外周组织的机制尚未得到评估，我们使用有限稀释分析来测量缺乏候选归巢分子的小鼠各种组织中 MCp 的浓度。 MCp 在小肠中几乎完全不存在，但存在于 β7 整合素缺陷小鼠的肺、脾、BM 和大肠中（在 C57BL/6 背景上），表明 β7 整合素对于这些细胞归巢至小肠至关重要。在缺乏 αE 整合素 (CD103)、β2 整合素 (CD18) 或重组激活基因 (RAG)-2 基因（单独或与白细胞介素 (IL) 受体共同伽马链组合）的小鼠组织中，MCp 浓度没有改变。因此，关键的是α4β7整合素而不是αEβ7整合素，并且淋巴细胞和自然杀伤细胞在基础条件下在指导MCp迁移中不起任何作用。当 BALB/c 小鼠中的 MCp 用亚致死剂量的 γ 射线消除，然后用同基因 BM 重建时，施用抗 α4 β7 整联蛋白、抗 α4 整联蛋白、抗 β7 整联蛋白或抗 MAdCAM-1 单克隆抗体 (mAb) 会阻断小肠中 MCp 的恢复。阻断性单克隆抗体可以在 BM 重建后 4 d 内施用，并具有最佳抑制作用，这意味着 MCp 必须首先在 BM 中产生，在脉管系统中循环，然后转移到肠道中。由于 MCp 保留在缺乏 β7 整合素和抗 α4 β7 整合素处理的小鼠的肺部，但不在小肠中，因此 α4 β7 整合素对于 MCp 在小肠（而非肺部）定位的组织特异性外渗至关重要。
Mast cells (MCs) are centrally important in allergic inflammation of the air-ways, as well as in the intestinal immune response to helminth infection. A single lineage of bone marrow (BM)-derived progenitors emigrates from the circulation and matures into phenotypically distinct MCs in different tissues. Because the mechanisms of MC progenitor (MCp) homing to peripheral tissues have not been evaluated, we used limiting dilution analysis to measure the concentration of MCp in various tissues of mice deficient for candidate homing molecules. MCp were almost completely absent in the small intestine but were present in the lung, spleen, BM, and large intestine of beta7 integrin-deficient mice (on the C57BL/6 background), indicating that a beta7 integrin is critical for homing of these cells to the small intestine. MCp concentrations were not altered in the tissues of mice deficient in the alphaE integrin (CD103), the beta2 integrin (CD18), or the recombination activating gene (RAG)-2 gene either alone or in combination with the interleukin (IL)-receptor common gamma chain. Therefore, it is the alpha4 beta7 integrin and not the alphaE beta7 integrin that is critical, and lymphocytes and natural killer cells play no role in directing MCp migration under basal conditions. When MCp in BALB/c mice were eliminated with sublethal doses of gamma -radiation and then reconstituted with syngeneic BM, the administration of anti-alpha4 beta7 integrin, anti-alpha4 integrin, anti-beta7 integrin, or anti-MAdCAM-1 monoclonal antibodies (mAbs) blocked the recovery of MCp in the small intestine. The blocking mAbs could be administered as late as 4 d after BM reconstitution with optimal inhibition, implying that the MCp must arise first in the BM, circulate in the vasculature, and then translocate into the intestine. Inasmuch as MCp are preserved in the lungs of beta7 integrin-deficient and anti-alpha4 beta7 integrin-treated mice but not in the small intestine, alpha4 beta7 integrin is critical for tissue specific extravasation for localization of MCp in the small intestine, but not the lungs.