ICMI 2015

F.11 DIFFERENTIAL REGULATION of INTESTINAL MACROPHAGE FUNCTION by INTERLEUKIN-10 and the GUT MICROBIOTA in the COLON versus the SMALL-BOWEL

Friday, July 17, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Elizabeth Mann, PhD , Johns Hopkins University, Baltimore 21202, MD, United States
Peter Andersen, PhD , Johns Hopkins University, Baltimore, MD
Dezhi Wang, MD , Johns Hopkins University, Baltimore, MD
Ying Dong, MD, PhD , Johns Hopkins University, Baltimore, MD
Weiwei Jiang, MD , Johns Hopkins University, Baltimore, MD
James Foster, PhD , Johns Hopkins University, Baltimore, MD
Daniel Peterson, PhD , Johns Hopkins University, Baltimore, MD
Xuhang Li, PhD , Johns Hopkins University, Baltimore, MD
Background: Macrophages (MФ) mediate intestinal immune tolerance. Interleukin (IL)-10 governs the regulatory functions of MФ; production of IL-10 by immune cells is induced by the gut microbiota. How MФ differ between the colon and small-bowel is poorly understood.

Methods: Colonic and small-bowel MФ from wildtype (WT), IL-10knockout (IL-10KO) and germ-free (GF) mice were analysed by flow cytometry/qPCR.

Results: Proportions of total MФ were enhanced in the colon compared to the small-bowel. Mature (MHC Class II+/Ly6C-) MФ expressed less ALDH1A2/ALDH1A3 in the colon, but colonic MФ favoured TGFβ/IL-1β expression. Colonic, but not small-bowel mature MФ showed decreased expression of TGFβ and ALDH1A2 in IL-10KO mice. Furthermore, inflammatory intermediary (MHC Class II+/Ly6C+) MФ accumulated in the colon, but not the small-bowel of IL-10KO mice. MФ in GF mice were predominantly mature MФ, with very few monocytes/intermediary MФ. These mature MФ in GF mice exhibited enhanced expression of cytokines IL-23/IL-6/TNFα and increased expression of the aryl-hydrocarbon receptor (for recognition of environmental antigens), alongside decreased expression of IL-10 and ALDH1A2. These differences were more striking in the small-bowel. MФ numbers in the MLN were increased in IL-10KO and GF mice, suggesting that IL-10 as well the microbiota may act to limit MФ migration from the intestine in the steady-state.

Conclusions: These data provide an important role for IL-10 in MФ-mediated immune tolerance in the colon in particular, and for the gut microbiota in MФ-mediated immune tolerance in the small-bowel. We are currently identifying the role of the microbiota in synergizing with IL-10 to regulate MФ homeostasis in the intestine.

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