Friday, July 17, 2015: 11:00 AM
Hall Berlin B, Ground Floor (Maritim Hotel)
Anna Bujko
,
CIR, Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway
Ole J. B. Landsverk
,
Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway
Lisa Gruber
,
Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway
Sheraz Yaqub
,
Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
Rune Horneland
,
Department for Transplantation Medicine, Oslo University Hospital, Oslo, Norway
Ole Øyen
,
Department for Transplantation Medicine, Oslo University Hospital, Oslo, Norway
Einar Martin Aandahl
,
Department for Transplantation Medicine, Oslo University Hospital, Oslo, Norway
Espen Bækkevold
,
Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway
Frode L. Jahnsen
,
Centre for Immune Regulation, Department of Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway
Tissue macrophages play a key role in preserving immune homeostasis in the gut mucosa by maintaining epithelial integrity, clearance of microorganisms and apoptotic material. As they also are key players in chronic inflammatory disorders, it is crucial to understand their origin and plasticity during steady state and inflammation.
We distinguished three subpopulations of CD45+HLA‑DR+CD14+ mononuclear phagocytes in normal small intestinal mucosa. Two subsets were calprotectin+CCR2+ with monocyte morphology. HLA‑DRintDC‑SIGN- monocytes produced much higher levels of multiple cytokines including TNFalpha, IL‑1beta and IL-6 compared with HLA‑DRhiDC-SIGN+ monocytes (both with and without LPS). Monocytes showed a gradual change towards morphologically mature macrophages that were DC‑SIGN+CD11c-calprotecin-CCR2- and produced no or very limited levels of cytokines even when challenged with LPS. However, they were highly phagocytic to soluble and particulate antigens. Examining transplanted human gut we found that monocytes were rapidly replaced, whereas mature macrophages showed delayed kinetics. However, one year post-transplantation all macrophages were also replaced.
Our findings demonstrate that blood CD14+ monocytes under homeostatic conditions constantly emigrate into the intestinal mucosa and differentiate into mature macrophages. Whereas recently recruited monocytes have strong proinflammatory properties, resident macrophages downregulate their capacity to produce cytokines but maintain their phagocytic capacity.
