title: Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis.
abstract: 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.
authors.affiliation: Institute of Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Shalapour
authors.forename: Katrin
authors.initials: K
authors.lastname: Deiser
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Rainer
authors.initials: R
authors.lastname: Glauben
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Krug
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.forename: Ozen
authors.initials: O
authors.lastname: Sercan
authors.forename: Stephane
authors.initials: S
authors.lastname: Chappaz
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
authors.forename: Daniela
authors.initials: D
authors.lastname: Finke
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.forename: Thomas
authors.initials: T
authors.lastname: Schüler
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D003092:Colitis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D016654:Genes, RAG-1 / Q000235:genetics; D006706:Homeostasis; D006965:Hyperplasia / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7