Commensal microflora and interferon-gamma promote steady-state interleukin-7 production in vivo.
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.
Shalapour
Shabnam
S
Institute of Immunology, Charité Campus Benjamin Franklin, Berlin, Germany.
Deiser
Katrin
K
Sercan
Ozen
O
Tuckermann
Jan
J
Minnich
Kerstin
K
Willimsky
Gerald
G
Blankenstein
Thomas
T
Hämmerling
Günter J
GJ
Arnold
Bernd
B
Schüler
Thomas
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D022202:Chromosomes, Artificial, Bacterial; D003907:Dexamethasone / Q000494:pharmacology; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D054892:Metagenome / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000900:Anti-Bacterial Agents; D015851:Interleukin-7; D008164:Luminescent Proteins; D003907:Dexamethasone; D007371:Interferon-gamma