IL-4 and TGF-β1 Counterbalance One Another while Regulating Mast Cell Homeostasis

被引：36
|
作者：
Macey, Matthew R. [1 ,2 ]
Sturgill, Jamie L. [2 ,3 ]
Morales, Johanna K. [1 ,2 ]
Falanga, Yves T. [1 ,2 ]
Morales, Joshua [1 ]
Norton, Sarah K. [2 ,3 ]
Yerram, Nitin [1 ,2 ]
Shim, Hoon [1 ,2 ]
Fernando, Josephine [1 ,2 ]
Gifillan, Alasdair M. [4 ]
Gomez, Gregorio [2 ,3 ]
Schwartz, Lawrence [2 ,3 ]
Oskeritzian, Carole [2 ,3 ]
Spiegel, Sarah [2 ,3 ]
Conrad, Daniel [2 ,3 ]
Ryan, John J. [1 ,2 ]
机构：
[1] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA
[2] Virginia Commonwealth Univ, Allergy & Allerg Dis Cooperat Res Ctr, Richmond, VA 23284 USA
[3] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA
[4] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA
来源：
JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 09期
基金：
美国国家卫生研究院;
关键词：
GROWTH-FACTOR-BETA; FC-EPSILON-RI; IGE RECEPTOR EXPRESSION; NECROSIS-FACTOR-ALPHA; T-CELLS; IN-VITRO; MEDIATOR RELEASE; ALLERGIC DISEASE; KIT EXPRESSION; STAT6; ISOFORM;
D O I：
10.4049/jimmunol.0903477
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Mast cell responses can be altered by cytokines, including those secreted by Th2 and regulatory T cells (Treg). Given the important role of mast cells in Th2-mediated inflammation and recent demonstrations of Treg-mast cell interactions, we examined the ability of IL-4 and TGF-beta 1 to regulate mast cell homeostasis. Using in vitro and in vivo studies of mouse and human mast cells, we demonstrate that IL-4 suppresses TGF-beta 1 receptor expression and signaling, and vice versa. In vitro studies demonstrated that IL-4 and TGF-beta 1 had balancing effects on mast cell survival, migration, and Fc epsilon RI expression, with each cytokine cancelling the effects of the other. However, in vivo analysis of peritoneal inflammation during Nippostrongylus brasiliensis infection in mice revealed a dominant suppressive function for TGF-beta 1. These data support the existence of a cytokine network involving the Th2 cytokine IL-4 and the Treg cytokine TGF-beta 1 that can regulate mast cell homeostasis. Dysregulation of this balance may impact allergic disease and be amenable to targeted therapy. The Journal of Immunology, 2010, 184: 4688-4695.
引用
收藏
页码：4688 / 4695
页数：8
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