TY - JOUR
T1 - Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis
AU - Shalapour, Shabnam
AU - Deiser, Katrin
AU - Kühl, Anja A.
AU - Glauben, Rainer
AU - Krug, Susanne M.
AU - Fischer, André
AU - Sercan, Özen
AU - Chappaz, Stephane
AU - Bereswill, Stefan
AU - Heimesaat, Markus M.
AU - Loddenkemper, Christoph
AU - Fromm, Michael
AU - Finke, Daniela
AU - Hämmerling, Günter J.
AU - Arnold, Bernd
AU - Siegmund, Britta
AU - Schüler, Thomas
PY - 2012/2/27
Y1 - 2012/2/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857510565&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0031939
DO - 10.1371/journal.pone.0031939
M3 - Article
AN - SCOPUS:84857510565
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e31939
ER -