TY - JOUR
T1 - Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine
AU - Ochi, Takanori
AU - Feng, Yongjia
AU - Kitamoto, Sho
AU - Nagao-Kitamoto, Hiroko
AU - Kuffa, Peter
AU - Atarashi, Koji
AU - Honda, Kenya
AU - Teitelbaum, Daniel H.
AU - Kamada, Nobuhiko
N1 - Funding Information:
This work was supported by JSPS Postdoctoral Fellowship for Research Abroad (to S.K. and H.N.-K.), the Crohn's and Colitis Foundation of America, Michigan Gastrointestinal Peptide Research Center NIDDK P30DK034933 (to N.K.), and NIH AI44076 (to D.H.T.).
PY - 2016/6/15
Y1 - 2016/6/15
N2 - Intestinal resident macrophages (MΦs) regulate gastrointestinal homeostasis via production of an anti-inflammatory cytokine interleukin (IL)-10. Although a constant replenishment by circulating monocytes is required to maintain the pool of resident MΦs in the colonic mucosa, the homeostatic regulation of MΦ in the small intestine (SI) remains unclear. Here, we demonstrate that direct stimulation by dietary amino acids regulates the homeostasis of intestinal MΦs in the SI. Mice that received total parenteral nutrition (TPN), which deprives the animals of enteral nutrients, displayed a significant decrease of IL-10-producing MΦs in the SI, whereas the IL-10-producing CD4+T cells remained intact. Likewise, enteral nutrient deprivation selectively affected the monocyte-derived F4/80+MΦ population, but not non-monocytic precursor-derived CD103+ dendritic cells. Notably, in contrast to colonic MΦs, the replenishment of SI MΦs and their IL-10 production were not regulated by the gut microbiota. Rather, SI MΦs were directly regulated by dietary amino acids. Collectively, our study highlights the diet-dependent, microbiota-independent regulation of IL-10-producing resident MΦs in the SI.
AB - Intestinal resident macrophages (MΦs) regulate gastrointestinal homeostasis via production of an anti-inflammatory cytokine interleukin (IL)-10. Although a constant replenishment by circulating monocytes is required to maintain the pool of resident MΦs in the colonic mucosa, the homeostatic regulation of MΦ in the small intestine (SI) remains unclear. Here, we demonstrate that direct stimulation by dietary amino acids regulates the homeostasis of intestinal MΦs in the SI. Mice that received total parenteral nutrition (TPN), which deprives the animals of enteral nutrients, displayed a significant decrease of IL-10-producing MΦs in the SI, whereas the IL-10-producing CD4+T cells remained intact. Likewise, enteral nutrient deprivation selectively affected the monocyte-derived F4/80+MΦ population, but not non-monocytic precursor-derived CD103+ dendritic cells. Notably, in contrast to colonic MΦs, the replenishment of SI MΦs and their IL-10 production were not regulated by the gut microbiota. Rather, SI MΦs were directly regulated by dietary amino acids. Collectively, our study highlights the diet-dependent, microbiota-independent regulation of IL-10-producing resident MΦs in the SI.
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U2 - 10.1038/srep27634
DO - 10.1038/srep27634
M3 - Article
C2 - 27302484
AN - SCOPUS:84974698763
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 27634
ER -