Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis

Shabnam Shalapour, Katrin Deiser, Anja A. Kühl, Rainer Glauben, Susanne M. Krug, André Fischer, Özen Sercan, Stephane Chappaz, Stefan Bereswill, Markus M. Heimesaat, Christoph Loddenkemper, Michael Fromm, Daniela Finke, Günter J. Hämmerling, Bernd Arnold, Britta Siegmund, Thomas Schüler

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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.

Original languageEnglish
Article numbere31939
JournalPLoS ONE
Issue number2
Publication statusPublished - 27 Feb 2012
Externally publishedYes

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