Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa
Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa
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DOI：
10.1152/ajpgi.00167.2003
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发表时间：
2004-03-01
影响因子：
4.5
通讯作者：
Ishii, H
中科院分区：
文献类型：
--
作者：
Hosoe, N;Miura, S;Ishii, H
最近有人提出，C-C趋化因子可能在淋巴细胞的器官特异性归巢中发挥作用，但在肠粘膜中没有足够的体内证据。本研究的目的是研究胸腺表达趋化因子（TECK）/CCL 25及其配体CCR 9是否参与T淋巴细胞与小鼠肠粘膜微血管的相互作用。荧光标记小肠T淋巴细胞，活体显微镜观察其与粘膜微血管的粘附。固有层淋巴细胞（LPL）和上皮内淋巴细胞（IEL）粘附于小肠和结肠，并且用TECK/CCL 25或抗TECK/CCL 25抗体脱敏CCR 9仅在小肠中显著抑制这些粘附。在这两个部位，TNF-α显著增加LPL粘附，但不增加IEL粘附。CCR 9或抗TECK/CCL 25抗体的脱敏也减弱了小肠中TNF-α诱导的LPL粘附。在小肠固有层中观察到TNF-α引起的TECK/CCL 25表达增加。因此，TECK/CCL 25可能在粘膜淋巴细胞粘附于小肠微血管而不是在非炎症和炎症条件下的结肠微血管中起重要作用。
It has recently been suggested that C-C chemokines may play a role in the organ-specific homing of lymphocytes, but there is not enough in vivo evidence in intestinal mucosa. The aim of this study was to examine whether thymus-expressed chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte interaction with microvessels of murine intestinal mucosa. T lymphocytes from the small intestine were fluorescence labeled, and their adhesion to mucosal microvessels was observed by intravital microscopy. Lamina proprial lymphocytes (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25 antibody significantly inhibited these adhesions only in small intestine. At both sites, TNF-alpha significantly increased LPL adhesion but not IEL adhesion. Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-alpha-induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25 by TNF-alpha was observed in the lamina propria of small intestine. TECK/CCL25 may thus play an important role in the adherence of mucosal lymphocytes to the microvessels of the small intestine but not the colon under uninflamed as well as inflamed conditions.