Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10

Y Ueda, H Kayama, SG Jeon, T Kusu… - International …, 2010 - academic.oup.com
Y Ueda, H Kayama, SG Jeon, T Kusu, Y Isaka, H Rakugi, M Yamamoto, K Takeda
International immunology, 2010academic.oup.com
Several subsets of innate immune cells, all with unique properties, reside within the
intestinal lamina propria. However, compared with intestinal dendritic cells (DCs), intestinal
macrophages are less well characterized. In this study, we examined the properties of
macrophages in the colonic lamina propria (LMϕ). Colonic DCs (LDC) showed LPS-induced
production of IL-12p40. In contrast, LMϕ showed constitutive IL-10 production and
unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the …
Abstract
Several subsets of innate immune cells, all with unique properties, reside within the intestinal lamina propria. However, compared with intestinal dendritic cells (DCs), intestinal macrophages are less well characterized. In this study, we examined the properties of macrophages in the colonic lamina propria (LMϕ). Colonic DCs (LDC) showed LPS-induced production of IL-12p40. In contrast, LMϕ showed constitutive IL-10 production and unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the gene expression profiles between LMϕ and LDC revealed that LMϕ preferentially expressed IL-10-related genes. LMϕ obtained from mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis factor (TNF)-α and IL-6 in response to LPS. IL-10 production in the large intestine was mainly induced by LMϕ and regulatory T cells and was dependent on the presence of commensal microbiota. Accordingly, LMϕ from germ-free mice showed less production of IL-10 and increased levels of LPS-induced TNF-α and IL-6 production. Taken together, these results demonstrate that the activity of LMϕ to produce pro-inflammatory cytokines is negatively regulated through commensal microbiota-dependent IL-10 production in the large intestine.
Oxford University Press