title: Increased CD40+ Fibrocytes in Patients With Idiopathic Orbital Inflammation.
abstract: OBJECTIVE
  To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells called fibrocytes in patients with idiopathic orbital inflammation (IOI).
  
  
  METHODS
  Seven patients with IOI were studied. In the 3 patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared with healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all 7 patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40, and collagen 1. Quantitation of CD40-mediated interleukin-6 (IL-6) production was measured using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n = 3). Fibrocytes are present in the peripheral blood of IOI patients (n = 7) but are scarce in healthy donors (n = 19). Fibrocytes from IOI patients express substantial levels of CD40, and ligation of CD40 increases IL-6 expression.
  
  
  CONCLUSIONS
  Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34(+) fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover, CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan; and Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, Michigan, U.S.A.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lee
authors.forename: Stephen
authors.initials: S
authors.lastname: Atkins
authors.forename: Anna
authors.initials: A
authors.lastname: Ginter
authors.forename: Victor M
authors.initials: VM
authors.lastname: Elner
authors.forename: Christine C
authors.initials: CC
authors.lastname: Nelson
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Douglas
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000473:pathology; D016727:Orbital Pseudotumor / Q000473:pathology*; D010641:Phenotype
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; D019013:CD40 Antigens; D024042:Collagen Type I; C508600:IL6 protein, human; D015850:Interleukin-6
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