Dach1 transcription factor regulates the expression of peripheral node addressin and lymphocyte trafficking in lymph nodes.
Dach1 transcription factor regulates the expression of peripheral node addressin and lymphocyte trafficking in lymph nodes.
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DOI：
10.1016/j.crimmu.2022.08.008
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发表时间：
2022
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淋巴细胞通过在血管和淋巴系统之间循环来调节免疫反应。高内皮小静脉，hev，表达选择性粘附分子的特殊血管，如PNAd和MAdCAM-1，介导naïve淋巴细胞从脉管系统迁移到淋巴结和Peyer's补丁。我们已经发现DACH1在发育中的hev型内皮细胞中大量表达。在胎儿晚期和新生儿早期，DACH1在淋巴结血管中的表达受限，与HEV的发展相对应。新生常规小鼠和血管特异性dach1缺陷小鼠淋巴结中MAdCAM-1+和CD34+内皮细胞比例降低。成年小鼠的dach1缺陷淋巴结显示PNAd+细胞比例较低，GFP转基因小鼠静脉注射淋巴细胞募集较少。这些发现表明，DACH1促进hev选择性粘附分子的表达，并介导淋巴细胞通过hev转运到淋巴结。高内皮小静脉（hev）以组织特异性的方式发育，并允许淋巴细胞运输。转录因子DACH1在发展中的淋巴结血管中表现出限制性表达模式。血管特异性dach1缺陷淋巴结表现出hev和淋巴细胞募集比例降低。
Lymphocytes regulate the immune response by circulating between the vascular and lymphatic systems. High endothelial venules, HEVs, special blood vessels expressing selective adhesion molecules, such as PNAd and MAdCAM-1, mediate naïve lymphocyte migration from the vasculature into the lymph nodes and Peyer's patches. We have identified that DACH1 is abundantly expressed in developing HEV-type endothelial cells. DACH1 showed a restricted expression pattern in lymph node blood vessels during the late fetal and early neonatal periods, corresponding to HEV development. The proportion of MAdCAM-1+ and CD34+ endothelial cells is reduced in the lymph nodes of neonatal conventional and vascular-specific Dach1-deficient mice. Dach1-deficient lymph nodes in adult mice demonstrated a lower proportion of PNAd+ cells and lower recruitment of intravenously administered lymphocytes from GFP transgenic mice. These findings suggest that DACH1 promotes the expression of HEV-selective adhesion molecules and mediates lymphocyte trafficking across HEVs into lymph nodes. The high endothelial venules, HEVs, develop in a tissue-specific manner and permit lymphocyte trafficking. The transcription factor DACH1 exhibit a restricted expression pattern in the blood vessels of developing lymph nodes. The blood vessel-specific Dach1-deficient lymph nodes exhibit a reduced proportion of HEVs and lymphocyte recruitment.