Papadakis K A, Prehn J, Moreno S T, Cheng L, Kouroumalis E A, Deem R, Breaverman T, Ponath P D, Andrew D P, Green P H, Hodge M R, Binder S W, Targan S R
Department of Medicine, Division of Gastroenterology and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Gastroenterology. 2001 Aug;121(2):246-54. doi: 10.1053/gast.2001.27154.
BACKGROUND & AIMS: Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the cognate chemokine receptor CCR9 predominate. We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease.
CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL. TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry.
The fraction of CCR9(+) T cells in inflamed SB was significantly lower than in uninvolved SB mucosa. In contrast, in peripheral blood lymphocytes, CCR9(+) lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's. Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates. TECK is not expressed in either normal or inflamed colon.
In SB immune-mediated diseases, there is repartitioning of CCR9(+) lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's. The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.
胸腺表达趋化因子(TECK)或CCL25在小肠中选择性表达,在固有层淋巴细胞(LPL)和表达同源趋化因子受体CCR9的上皮内白细胞占优势的部位。我们对TECK和表达CCR9的淋巴细胞在小肠克罗恩病中的作用进行了特征分析。
通过流式细胞术和对LPL进行Northern印迹分析固有层、肠系膜淋巴结和外周血淋巴细胞上CCR9的表达。通过逆转录聚合酶链反应和免疫组织化学分析炎症性小肠和结肠中TECK的表达。
炎症性小肠中CCR9(+) T细胞的比例显著低于未受累的小肠黏膜。相反,在外周血淋巴细胞中,小肠克罗恩病或乳糜泻患者的CCR9(+)淋巴细胞明显升高,但纯结肠克罗恩病患者则不然。此外,炎症性小肠中TECK的表达发生改变,在靠近淋巴细胞浸润的隐窝上皮细胞中呈斑片状强烈表达。正常或炎症性结肠中均不表达TECK。
在小肠免疫介导的疾病中,CCR9(+)淋巴细胞在小肠和血液之间重新分布,且小肠克罗恩病中TECK的表达模式发生改变。TECK/CCR9配体/受体对可能在小肠克罗恩病的发病机制中起重要作用。