title: HLA-DR(hi) and CCR9 Define a Pro-Inflammatory Monocyte Subset in IBD.
abstract: OBJECTIVE
  It has been demonstrated that circulating monocytes relocate to the intestinal mucosa during intestinal inflammation, but the phenotype and inflammatory mechanisms of these monocytes remain poorly understood. Here, we have investigated blood monocytes expressing high levels of HLA-DR 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-DR(hi) 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-DR(hi) 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-DR(hi) monocytes was significantly reduced. CD14(+)HLA-DR(hi) 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-DR(hi) 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.
authors.affiliation: Department of Medicine, Translational Immunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ludvig
authors.initials: L
authors.lastname: Linton
authors.forename: Mats
authors.initials: M
authors.lastname: Karlsson
authors.forename: Jeanette
authors.initials: J
authors.lastname: Grundström
authors.forename: Eric
authors.initials: E
authors.lastname: Hjalmarsson
authors.forename: Annelie
authors.initials: A
authors.lastname: Lindberg
authors.forename: Emma
authors.initials: E
authors.lastname: Lindh
authors.forename: Hans
authors.initials: H
authors.lastname: Glise
authors.forename: Ragnar
authors.initials: R
authors.lastname: Befrits
authors.forename: Izabella
authors.initials: I
authors.lastname: Janczewska
authors.forename: Per
authors.initials: P
authors.lastname: Karlén
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Michael
authors.initials: M
authors.lastname: Eberhardson