TY - JOUR
T1 - Commensal microflora and interferon-γ promote steady-state interleukin-7 production in vivo
AU - Shalapour, Shabnam
AU - Deiser, Katrin
AU - Sercan, Özen
AU - Tuckermann, Jan
AU - Minnich, Kerstin
AU - Willimsky, Gerald
AU - Blankenstein, Thomas
AU - Hämmerling, Günter J.
AU - Arnold, Bernd
AU - Schüler, Thomas
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Commensal microflora
KW - IFN-cγ
KW - IL-7
KW - Intestinal epithelial cells
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U2 - 10.1002/eji.201040441
DO - 10.1002/eji.201040441
M3 - Article
C2 - 20690180
AN - SCOPUS:77956478866
SN - 0014-2980
VL - 40
SP - 2391
EP - 2400
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 9
ER -