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

Shabnam Shalapour; Katrin Deiser; Ozen Sercan; Jan Tuckermann; Kerstin Minnich; Gerald Willimsky; Thomas Blankenstein; Günter J Hämmerling; Bernd Arnold; Thomas Schüler

doi:10.1002/eji.201040441

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

Eur J Immunol. 2010 Sep;40(9):2391-400. doi: 10.1002/eji.201040441.

Authors

Shabnam Shalapour¹, Katrin Deiser, Ozen Sercan, Jan Tuckermann, Kerstin Minnich, Gerald Willimsky, Thomas Blankenstein, Günter J Hämmerling, Bernd Arnold, Thomas Schüler

Affiliation

¹ Institute of Immunology, Charité Campus Benjamin Franklin, Berlin, Germany.

PMID: 20690180
DOI: 10.1002/eji.201040441

Abstract

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-gamma and the commensal microflora promote steady-state IL-7 production in the intestine. Furthermore, we demonstrate that the blockade of IFN-gamma signaling in intestinal epithelial cells strongly reduces their IFN-gamma-driven IL-7 production. In summary, our data suggest a feedback loop in which commensal bacteria drive IFN-gamma production by lymphocytes, which in turn promotes epithelial cell IL-7 production and the survival of IL-7-dependent lymphocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage
Cell Line, Tumor
Cell Survival / drug effects
Cell Survival / genetics
Cell Survival / immunology
Chromosomes, Artificial, Bacterial
Dexamethasone / pharmacology
Feedback, Physiological
Gene Expression Regulation / drug effects
Gene Expression Regulation / immunology
Interferon-gamma / genetics
Interferon-gamma / immunology
Interferon-gamma / metabolism*
Interleukin-7 / genetics
Interleukin-7 / immunology
Interleukin-7 / metabolism*
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

Substances

Anti-Bacterial Agents
Interleukin-7
Luminescent Proteins
Dexamethasone
Interferon-gamma