HLA-DRhi and CCR9 Define a Pro-Inflammatory Monocyte Subset in IBD

Abstract

R and CCR9 in patients with inflammatory bowel disease (IBD). METHODS: Fifty-one patients with mild to severe ulcerative colitis (UC;n=31; UC-DAI 3–12) or Crohn's disease (CD;n=20; Harvey–Bradshaw indices (HBI) 2–16) were included together with 14 controls, during IBD therapy for four consecutive weeks. The frequency of CD14+HLA-DRhi monocytes was monitored weekly in peripheral blood, using flow cytometry. The surface phenotype and cytokine profile of these monocytes were established using flow cytometry and real-time PCR. Clinical parameters were assessed weekly in all patients. RESULTS: The frequency of circulating CD14+HLA-DRhi monocytes was significantly higher in IBD patients with moderate to severe disease compared with healthy controls (P<0.001). During treatment with corticosteroids and granulocyte/monocyte apheresis, the proportion of circulating CD14+HLA-DRhi monocytes was significantly reduced. CD14+HLA-DRhi monocytes produced high levels of inflammatory mediators, such as tumor necrosis factor (TNF)-α, and expressed the gut-homing receptor CCR9. Furthermore, we found that the CCR9 ligand, CCL25/TECK, was expressed at high levels in the colonic mucosa in IBD patients with active disease. CONCLUSIONS: CD14+HLA-DRhi blood monocytes were increased in patients with active IBD. These monocytes exhibit a pro-inflammatory, gut-homing phenotype with regard to their TNF-α production and expression of CCR9. Our results suggest that these monocytes are important in mediating intestinal inflammation, and provide potential therapeutic targets in IBD. *Correspondence: L Linton, MSc, Department of Medicine, Translational Immunology Unit, Karolinska Institutet, SE-171 76 Stockholm, Sweden. E-mail: ludvig.linton@ki.se Received 27 June 12; revised 27 September 12; accepted 1 November 12 published online 20 December 2012 © 2012 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology...