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K. I. Papageorgiou, R. Beaubien, R. S. Douglas, T. J. Smith; Activation of Human Circulating Fibrocytes Through CD40 Induces Results in the Induction of Potent Proinflammatory and Chemoattractant Cytokines. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3927.
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© ARVO (1962-2015); The Authors (2016-present)
Fibrocytes are circulating fibroblast precursors that traffic to sites of inflammation and fibrosis. They are markedly more frequent in patients with Graves' disease and accumulate in thyroid-associated ophthalmopathy (TAO). CD40 and its cognate ligand CD154 comprise an important activational pathway involved in the pathogenesis of several autoimmune diseases. Here we investigated CD40 expression on fibrocytes and its role in upregulating cytokine production.
Human circulating fibrocytes were obtained from donors with TAO and controls. Following 14 days in culture, fibrocytes were incubated with CD154-expressing insect membranes or control membranes. Cytokine production was evaluated with bead immunoassay (Luminex).
Fibrocytes display the CD40 costimulatory protein. Its activation leads to significant upregulation of several cytokines. Specific IL-6, IL-8 and TNF-a production are upregulated by 186-fold, 17-fold and 937-fold, respectively. CD154 induced IL-6 from 20 pg/ml to 3899 pg/ml, IL-8 from 2005 pg/ml to 34006 pg/ml, and TNF-a from 4 pg/ml to 3748 pg/ml.
CD40 display and activation by CD154 on circulating human fibrocytes induces IL-6, IL-8 and TNF-a. These findings support the concept that cognate interactions between infiltrating fibrocytes and T lymphocytes through the CD40-CD154 pathway may promote the tissue remodeling observed in TAO. Disruption of this pathway could represent an effective strategy for treating active TAO.
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