Commensal microflora and interferon-γ promote steady-state interleukin-7 production in vivo

• Published in: European journal of immunology 2010-09, Vol.40 (9), p.2391-2400
• Main Authors: Shalapour, Shabnam, Deiser, Katrin, Sercan, Özen, Tuckermann, Jan, Minnich, Kerstin, Willimsky, Gerald, Blankenstein, Thomas, Hämmerling, Günter J, Arnold, Bernd, Schüler, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - genetics; Cell Survival - immunology; Chromosomes, Artificial, Bacterial; Commensal microflora; Dexamethasone - pharmacology; Feedback, Physiological; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; IFN‐γ; IL‐7; Interferon-gamma - genetics; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-7 - genetics; Interleukin-7 - immunology; Interleukin-7 - metabolism; Intestinal epithelial cells; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestines - drug effects; Intestines - microbiology; Intestines - pathology; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Metagenome - drug effects; Metagenome - immunology; Mice; Mice, Transgenic; Signal Transduction - drug effects; Signal Transduction - genetics; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040441

IL-7 is a major regulator of lymphocyte homeostasis; however, little is known about the mechanisms that regulate IL-7 production. To study Il7 gene regulation in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive quantification of Il7 gene activity in live mice and, additionally, the simultaneous activation/inactivation of target genes in IL-7-producing cells. With these IL-7-reporter mice, we identify thymus, skin and intestine as major sources of IL-7 in vivo. Importantly, we show that IFN-γ and the commensal microflora promote steady-state IL-7 production in the intestine. Furthermore, we demonstrate that the blockade of IFN-γ signaling in intestinal epithelial cells strongly reduces their IFN-γ-driven IL-7 production. In summary, our data suggest a feedback loop in which commensal bacteria drive IFN-γ production by lymphocytes, which in turn promotes epithelial cell IL-7 production and the survival of IL-7-dependent lymphocytes.