Monocyte chemoattractant protein-1 contributes to gut homeostasis and intestinal inflammation by composition of IL-10-producing regulatory macrophage subset

Yasuhiro Takada, Tadakazu Hisamatsu, Nobuhiko Kamada, Mina T. Kitazume, Haruki Honda, Yosuke Oshima, Riko Saito, Tetsuro Takayama, Taku Kobayashi, Hiroshi Chinen, Yohei Mikami, Takanori Kanai, Susumu Okamoto, Toshifumi Hibi

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Lamina propria macrophages (LPMφs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMφs produced large amounts of MCP-1, even in a steady state. MCP-1 deficiency caused impaired IL-10 production by LPMφs and led to exacerbation of dextran sulfate sodium-induced acute colitis. As an explanation of this impaired IL-10 production by LPMφs, we found that LPMφs could be separated into two subsets with distinct side-scattered properties, namely LPMφ1 (CD11b+F4/80 +CD11c-SSChi) and LPMf2 (CD11b +F4/80+CD11c-SSClo). Unlike LPMφ1, the LPMφ2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria. LPMφs isolated from MCP-1-deficient mice produced less IL-10 as a consequence of the lack of the MCP-1-dependent LPMφ2 population. This imbalanced composition in LPMφ population may be involved in the susceptibility to DSS-induced colitis in MCP-1-deficient mice. Our results suggest that endogenous MCP-1 contributes to the composition of resident LPMφ subsets in the intestine. Moreover, MCP-1-dependent LPMφ2 subset may play an important role in maintenance of gut homeostasis in the steady state, and in the termination of excess inflammatory responses in the intestine, by producing IL-10.

Original languageEnglish
Pages (from-to)2671-2676
Number of pages6
JournalJournal of Immunology
Volume184
Issue number5
DOIs
Publication statusPublished - 2010 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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