title: Reduced numbers of mucosal DR(int) macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-α treatment in patients with Crohn's disease.
abstract: OBJECTIVE
  Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood.
  
  
  METHODS
  Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DR(int) and CD14 (+) DR(hi) MQs, CD141(+), CD141(-) and CD103(+) DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry.
  
  
  RESULTS
  At baseline, we observed higher numbers of DR(int) MQs and lower numbers of CD103(+) DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR(int) MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+) DCs increased [9-20 × 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4.
  
  
  CONCLUSIONS
  In CD, mucosal inflammation is associated with high numbers of DR(int) MQs and low numbers of CD103(+) DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR(int) MQs play a pivotal role in CD inflammation.
authors.affiliation: a Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark ;
authors.forename: Anders
authors.initials: A
authors.lastname: Dige
authors.affiliation: b Department of Microbiology and Immunology , Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ;|c Department of Internal Medicine and Clinical Nutrition , Institute for Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Magnusson
authors.affiliation: b Department of Microbiology and Immunology , Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ;|c Department of Internal Medicine and Clinical Nutrition , Institute for Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Öhman
authors.affiliation: a Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark ;
authors.forename: Christian Lodberg
authors.initials: CL
authors.lastname: Hvas
authors.affiliation: a Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark ;
authors.forename: Jens
authors.initials: J
authors.lastname: Kelsen
authors.affiliation: b Department of Microbiology and Immunology , Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ;
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Wick
authors.affiliation: a Gastro-Immuno Research Laboratory (GIRL), Department of Hepatology and Gastroenterology , Aarhus University Hospital , Aarhus , Denmark ;
authors.forename: Jørgen
authors.initials: J
authors.lastname: Agnholt
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D039001:Integrin alpha Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015415:Biomarkers; D039001:Integrin alpha Chains; C091367:alpha E integrins; D000068879:Adalimumab
keywords: Adalimumab; Crohn’s disease; anti-TNF-α treatment; dendritic cell; macrophage