Interleukin-7 Links T Lymphocyte and Intestinal Epithelial Cell Homeostasis

被引:34
|
作者
Shalapour, Shabnam [1 ]
Deiser, Katrin [1 ]
Kuehl, Anja A. [2 ]
Glauben, Rainer [3 ]
Krug, Susanne M. [4 ]
Fischer, Andre [5 ]
Sercan, Oezen [1 ,6 ]
Chappaz, Stephane [7 ]
Bereswill, Stefan [5 ]
Heimesaat, Markus M. [5 ]
Loddenkemper, Christoph [2 ]
Fromm, Michael [4 ]
Finke, Daniela [7 ]
Haemmerling, Guenter J. [6 ]
Arnold, Bernd [6 ]
Siegmund, Britta [3 ]
Schueler, Thomas [1 ,6 ]
机构
[1] Charite, Inst Immunol, D-13353 Berlin, Germany
[2] Charite, Res Ctr ImmunoSci, Inst Pathol, D-13353 Berlin, Germany
[3] Charite, Dept Gastroenterol Infectiol & Rheumatol, D-13353 Berlin, Germany
[4] Charite, Inst Clin Physiol, D-13353 Berlin, Germany
[5] Charite, Inst Microbiol & Hyg, D-13353 Berlin, Germany
[6] German Canc Res Ctr, Dept Mol Immunol, D-6900 Heidelberg, Germany
[7] Univ Basel, Div Dev Immunol, Dept Biomed, Basel, Switzerland
来源
PLOS ONE | 2012年 / 7卷 / 02期
基金
瑞士国家科学基金会;
关键词
CHRONIC COLITIS; TRANSGENIC MICE; BETA-CATENIN; IN-VIVO; IL-7; INNATE; INFLAMMATION; RECEPTOR; DIFFERENTIATION; PROLIFERATION;
D O I
10.1371/journal.pone.0031939
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Interleukin-7 (IL-7) is a major survival factor for mature T cells. Therefore, the degree of IL-7 availability determines the size of the peripheral T cell pool and regulates T cell homeostasis. Here we provide evidence that IL-7 also regulates the homeostasis of intestinal epithelial cells (IEC), colon function and the composition of the commensal microflora. In the colon of T cell-deficient, lymphopenic mice, IL-7-producing IEC accumulate. IEC hyperplasia can be blocked by IL-7-consuming T cells or the inactivation of the IL-7/IL-7R signaling pathway. However, the blockade of the IL-7/IL-7R signaling pathway renders T cell-deficient mice more sensitive to chemically-induced IEC damage and subsequent colitis. In summary, our data demonstrate that IL-7 promotes IEC hyperplasia under lymphopenic conditions. Under non-lymphopenic conditions, however, T cells consume IL-7 thereby limiting IEC expansion and survival. Hence, the degree of IL-7 availability regulates both, T cell and IEC homeostasis.
引用
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页数:11
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