A functional role for CCR6 on proallergic T cells in the gastrointestinal tract.
A functional role for CCR6 on proallergic T cells in the gastrointestinal tract.
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DOI：
10.1053/j.gastro.2009.09.016
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发表时间：
2010-01
期刊：
影响因子：
29.4
通讯作者：
Berin MC
中科院分区：
文献类型：
--
作者：
Blázquez AB;Knight AK;Getachew H;Bromberg JS;Lira SA;Mayer L;Berin MC
CCL20是一种趋化因子，调节白细胞向小肠的稳态和炎症运输，并调节胃肠道淋巴结构的发育。表达Th2细胞因子的T细胞对实验性食物过敏至关重要，我们假设CCL20参与了这些细胞在肠道的定位。我们用CCR6+/+和−/−小鼠评价了CCR6在致敏和口服卵清蛋白攻击所致变态反应性腹泻中的作用。CCR6−/−小鼠在卵清蛋白诱导的腹泻中受到保护，但令人惊讶的是，肥大细胞增多症或过敏原特异性IgE没有受到损害。CCR6CD3抗体对−/−小鼠T细胞介导的腹泻也有保护作用。过敏性腹泻与肠粘膜内Th2型细胞因子的表达增加有关，而在CCR6−/−小鼠中这种细胞因子的表达显著减少。FTY720治疗对淋巴细胞归巢的抑制并没有损害过敏性腹泻，这表明T细胞可以在小肠内局部重新激活。最后，T细胞转移研究表明，CCR6在被转移的T细胞和受体小鼠身上都是必需的，才能在胃肠道表现出过敏疾病。这些研究强调了携带CCR6的T细胞在胃肠道变态反应疾病的发病机制中的肥大细胞和IgE不依赖的作用。
CCL20 is a chemokine that regulates the homeostatic and inflammatory trafficking of leukocytes to the small intestine, and regulates the development of the gastrointestinal lymphoid architecture. T cells expressing Th2 cytokines are critical for experimental food allergy, and we hypothesized that CCL20 is involved in the localization of these cells to the gut. We evaluated the role of CCR6 in allergic diarrhea induced by sensitization and oral challenge with ovalbumin (OVA) using CCR6+/+ and −/− mice. CCR6−/− mice were protected from OVA-induced diarrhea, but surprisingly were not impaired in mastocytosis or allergen-specific IgE. CCR6−/− mice were also protected from T cell-mediated diarrhea induced by anti-CD3 antibody. Allergic diarrhea was associated with an increased expression of Th2 cytokines within the intestinal mucosa that was significantly reduced in CCR6 −/− mice. Inhibition of lymphocyte homing by treatment with FTY720 did not impair allergic diarrhea, indicating that reactivation of T cells could occur locally within the small intestine. Finally, T cell transfer studies demonstrated that CCR6 was required both on the transferred T cells and in the recipient mouse in order to manifest allergic disease in the gastrointestinal tract. These studies highlight a mast cell- and IgE-independent role for CCR6-bearing T cells in the pathogenesis of gastrointestinal allergic disease.
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影响因子：
6
作者：
McDonald, Keely G.;McDonough, Jacquelyn S.;Newberry, Rodney D.
通讯作者：
Newberry, Rodney D.
DOI：
10.1152/ajpgi.00496.2005
发表时间：
2006-08-01
影响因子：
4.5
作者：
Fujii, R.;Kanai, T.;Watanabe, M.
通讯作者：
Watanabe, M.
DOI：
10.1084/jem.194.12.1875
发表时间：
2001-12-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Henning G;Ohl L;Junt T;Reiterer P;Brinkmann V;Nakano H;Hohenberger W;Lipp M;Förster R
通讯作者：
Förster R
DOI：
10.1152/ajpgi.2001.280.4.g710
发表时间：
2001-04-01
影响因子：
4.5
作者：
Izadpanah, A;Dwinell, MB;Kagnoff, MF
通讯作者：
Kagnoff, MF
影响因子：
4.4
作者：
Hamada, H;Hiroi, T;Ishikawa, H
通讯作者：
Ishikawa, H