Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine.
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.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.|Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Takanori
T
Ochi
Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Yongjia
Y
Feng
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Sho
S
Kitamoto
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Hiroko
H
Nagao-Kitamoto
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Peter
P
Kuffa
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
Koji
K
Atarashi
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
Kenya
K
Honda
Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
Daniel H
DH
Teitelbaum
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Nobuhiko
N
Kamada
D000596:Amino Acids / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D006706:Homeostasis; D039001:Integrin alpha Chains / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism* / Q000382:microbiology; D054390:Receptors, CCR2 / Q000378:metabolism
D000596:Amino Acids; D015703:Antigens, CD; D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; C556062:IL10 protein, mouse; D039001:Integrin alpha Chains; D054390:Receptors, CCR2; C091367:alpha E integrins; D016753:Interleukin-10