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Reduced numbers of mucosal DRint macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-alpha treatment in patients with Crohn's disease

Journal article
Authors A. Dige
Maria K Magnusson
Lena Öhman
C. L. Hvas
J. Kelsen
Mary Jo Wick
J. Agnholt
Published in Scandinavian Journal of Gastroenterology
Volume 51
Issue 6
Pages 692-699
ISSN 0036-5521
Publication year 2016
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 692-699
Language en
Keywords anti-TNF-alpha treatment, dendritic cell, Crohn's disease, macrophage, Adalimumab, inflammatory-bowel-disease, ulcerative-colitis, infliximab therapy, gene-expression, blood monocytes, lamina propria, activity index, t-cells, pathogenesis, activation, Gastroenterology & Hepatology
Subject categories Gastroenterology and Hepatology


Objective Anti-TNF-alpha 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-alpha antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. Material and 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 (+) DRint and CD14 (+) DRhi 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 DRint 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 x 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DRint MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+ )DCs increased [9-20 x 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 DRint MQs and low numbers of CD103(+ )DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-alpha treatment. These results suggest that DRint MQs play a pivotal role in CD inflammation.

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