CCR6 marks regulatory T cells as a colon-tropic, IL-10-producing phenotype.
CCR6 marks regulatory T cells as a colon-tropic, IL-10-producing phenotype.
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DOI：
10.4049/jimmunol.1001156
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Kelsall BL
中科院分区：
文献类型：
--
作者：
Kitamura K;Farber JM;Kelsall BL
CCR6及其配体CCL20在患有炎症性肠病的人和实验性结肠炎的小鼠的结肠中表达增加，但它们在疾病发病机制中的作用尚不清楚。在结肠炎的T细胞转移模型中，我们证明了CCR6对调节性T (Treg)3细胞的作用。与给予WT细胞的小鼠相比，给予Ccr6−/−CD4+CD45RBhigh T细胞的Rag2−/−小鼠结肠炎更严重，产生IFN-γ的T细胞增加。虽然在两组的肠系膜淋巴结和结肠中观察到相同频率的诱导/获得性Treg （iTreg）细胞，但Ccr6−/−iTreg细胞的抑制能力受损。WT或Ccr6−/−Treg细胞与CD4+CD45RBhigh T细胞的共转移研究也显示了Ccr6−/−Treg细胞抑制的缺陷。CCR6+ Treg细胞在稳定状态下具有抗原活化和il -10产生的特征，在炎症期间优先迁移到结肠。因此，我们得出结论，在结肠炎T细胞转移模型中，CCR6在Treg细胞上的表达是Treg细胞介导的抑制发挥全部功能所必需的。CCR6可能通过向发炎的结肠募集抗原特异性、产生il -10的iTreg细胞来调节结肠炎。
Expression of CCR6 and its ligand, CCL20, are increased in the colon of humans with inflammatory bowel diseases and mice with experimental colits, however their role in disease pathogenesis remains obscure. Here we demonstrate a role for CCR6 on regulatory T (Treg)3 cells in the T cell-transfer model of colitis. Rag2−/− mice given Ccr6−/− CD4+CD45RBhigh T cells had more severe colitis with increased IFN-γ-producing T cells, compared to the mice given WT cells. While equivalent frequency of induced/acquired Treg (iTreg) cells was observed in mesenteric lymph nodes and colon from both groups, the suppressive capacity of Ccr6−/− iTreg cells was impaired. Co-transfer studies of WT or Ccr6−/− Treg cells with CD4+CD45RBhigh T cells also showed the defect of Ccr6−/− Treg cell suppression. CCR6+ Treg cells were characterized as antigen-activated and IL-10-producing in the steady state, and preferentially migrated to the colon during inflammation. Thus, we concludes that CCR6 expression on Treg cells was required for the full function of Treg cell-mediated suppression in the T cell-transfer model of colitis. CCR6 may contribute to the regulation of colitis via the recruitment of antigen-specific, IL-10-producing iTreg cells to the inflamed colon.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
影响因子：
6
作者：
Baumforth, Karl R. N.;Birgersdotter, Anna;Murray, Paul G.
通讯作者：
Murray, Paul G.
DOI：
10.1152/ajpgi.00409.2006
发表时间：
2007-05-01
影响因子：
4.5
作者：
Katchar, Kianoosh;Kelly, Ciaran P.;Keates, Andrew C.
通讯作者：
Keates, Andrew C.