Increased CD40+ Fibrocytes in Patients With Idiopathic Orbital Inflammation

Ophthalmic Plast Reconstr Surg. 2015 May-Jun;31(3):202-6. doi: 10.1097/IOP.0000000000000243.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Antigens, CD34 / metabolism
  • CD40 Antigens / metabolism*
  • Cells, Cultured
  • Collagen Type I / metabolism
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Orbit / pathology
  • Orbital Pseudotumor / pathology*
  • Phenotype

Substances

  • ACTA2 protein, human
  • Actins
  • Antigens, CD34
  • CD40 Antigens
  • Collagen Type I
  • IL6 protein, human
  • Interleukin-6