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Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

Ahadome, SD; Mathew, R; Reyes, NJ; Mettu, PS; Cousins, SW; Calder, VL; Saban, DR; (2016) Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy. JCI Insight , 1 (12) , Article e87012. 10.1172/jci.insight.87012. Green open access

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Abstract

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b(+) DC-derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism.

Type: Article
Title: Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/jci.insight.87012
Publisher version: http://dx.doi.org/10.1172/jci.insight.87012
Language: English
Additional information: Copyright © 2016, American Society for Clinical Investigation. This is an Open Access article.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1514825
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