ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection.
ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection.
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DOI：
10.1002/eji.201242794
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发表时间：
2013-03
影响因子：
5.4
通讯作者：
Taylor, Matthew D.
中科院分区：
文献类型：
--
作者：
Redpath, Stephen A.;van der Werf, Nienke;Cervera, Ana M.;MacDonald, Andrew S.;Gray, David;Maizels, Rick M.;Taylor, Matthew D.
关键词：
Foxp3+ 调节性 T (Treg) 细胞是蠕虫感染期间的关键免疫调节因子，确定其诱导机制对于设计蠕虫感染、过敏和自身免疫的治疗方法至关重要。关于蠕虫感染期间有利于 Foxp3+ Treg 细胞反应发展的共刺激环境，目前知之甚少。由于最近的证据表明共刺激受体 ICOS 在定义 Foxp3+ Treg 细胞功能中，我们研究了 ICOS 在蠕虫诱导的 Foxp3+ Treg 细胞反应中的作用。 ICOS−/− 小鼠感染 Heligmosomoides polygyrus 或 Schistosoma mansoni 导致 Foxp3+ Treg 细胞的扩增和维持减少。此外，在 H. polygyrus 感染期间，ICOS 缺陷导致 Foxp3+ Treg 细胞凋亡增加、Foxp3+ Treg 细胞 IL-10 产生特异性受损，以及无法在肠固有层内产生假定的适应性 Helios−Foxp3+ Treg 细胞反应。固有层 Foxp3+ Treg 细胞反应受损与 CD4+ T 细胞产生的 IL-4 和 IL-13 增加有关，表明 ICOS 主要下调感染部位的 2 型反应，与其在淋巴组织内促进 2 型反应形成鲜明对比。因此，ICOS 以组织特异性方式调节 2 型免疫，并在蠕虫感染期间驱动 Foxp3+ Treg 细胞扩增和功能中发挥关键作用。
Foxp3+ regulatory T (Treg) cells are key immune regulators during helminth infections, and identifying the mechanisms governing their induction is of principal importance for the design of treatments for helminth infections, allergies and autoimmunity. Little is yet known regarding the co-stimulatory environment that favours the development of Foxp3+ Treg-cell responses during helminth infections. As recent evidence implicates the co-stimulatory receptor ICOS in defining Foxp3+ Treg-cell functions, we investigated the role of ICOS in helminth-induced Foxp3+ Treg-cell responses. Infection of ICOS−/− mice with Heligmosomoides polygyrus or Schistosoma mansoni led to a reduced expansion and maintenance of Foxp3+ Treg cells. Moreover, during H. polygyrus infection, ICOS deficiency resulted in increased Foxp3+ Treg-cell apoptosis, a Foxp3+ Treg-cell specific impairment in IL-10 production, and a failure to mount putatively adaptive Helios−Foxp3+ Treg-cell responses within the intestinal lamina propria. Impaired lamina propria Foxp3+ Treg-cell responses were associated with increased production of IL-4 and IL-13 by CD4+ T cells, demonstrating that ICOS dominantly downregulates Type 2 responses at the infection site, sharply contrasting with its Type 2-promoting effects within lymphoid tissue. Thus, ICOS regulates Type 2 immunity in a tissue-specific manner, and plays a key role in driving Foxp3+ Treg-cell expansion and function during helminth infections.
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DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C
影响因子：
4.4
作者：
Akbari, Omid;Stock, Philippe;DeKruyff, Rosemarie H.
通讯作者：
DeKruyff, Rosemarie H.