(A and B) Uniquely high aldehyde dehydrogenase (ALDH) activity of CD11b⁺ (11b) BM-derived DCs (BMDC), relative to CD103⁺ (103) BMDCs. (C) CD11b⁺ BMDC-derived ALDH impairs normal fibroblast proliferation and contractility in vitro. Primary conjunctival fibroblasts were plated in media for the proliferation assay or a free-floating collagen matrix for the contractility assay. Added to the wells were complete media only, conditioned media from CD11b⁺ BMDCs treated with or without diethylaminobenzaldehyde (DEAB), or conditioned media from CD103⁺ BMDCs as indicated. Gel contraction and proliferation was measured 1 d later. (D) Retinoid x receptor (RXR) signaling is responsible for CD11b⁺ BMDC-derived ALDH impairment of normal fibroblast contractility and proliferation. Fibroblasts were plated in the presence of CD11b⁺ BMDC-conditioned media or not and treated with RXR or retinoic acid receptor (RAR) inhibitor as indicated. (E) 9-cis-RA (9c) mediates RXR signaling that causes impairment of normal fibroblast contractility and proliferation. Primary conjunctival fibroblasts were plated, and some samples received 9c or all-trans-RA (AT), in addition to RXR inhibitor as indicated. (F) RXR agonist, bexarotene (Bex), impairs normal fibroblast contractility and proliferation (Veh, vehicle). (G) Local administration of Bex in vivo induces ocular mucosal fibrosis. Subconjunctival injection of Bex (10 ng) was administered to one eye, whereas the vehicle control was injected into the fellow eye. Clinical images were obtained, and Masson’s trichrome–stained sections of the conjunctiva were assessed (white arrows indicate diseased eye; black arrows indicate subepithelial collagen deposition). Triplicate data points represent fibroblast data from 3 separate fibroblast cultures from 3 different mice (error bars represent ±SEM, ***P < 0.0005, ****P < 0.00005, 1-way ANOVA with Bonferroni correction). In vivo data are representative of n = 5 mice. Each experiment was carried out at least twice.