Conjunctival Goblet Cells modulate dendritic cell maturation and retinoic acid producing capacity

摘要

Purpose : Conjunctival goblet cells (GC) produce an array of factors that support and protect the ocular surface. They are in close proximity to antigen presenting dendritic cells (DC) in the epithelium and stroma that initiate adaptive immune response and maintain tolerance. Loss of GCs is associated with chronic severe ocular surface inflammation. The objective of this study was to determine if conjunctival goblet cells condition bone marrow derived DCs with tolerogenic properties that are associated with maintaining mucosal immune homeostasis. Methods : Bone marrow derived DCs (BMDCs) were exposed to GC conditioned or control media with or without lipopolysaccharide (LPS) and DC maturation (MHC-II, CD86), inflammatogenic (IL-1?2, IL-12, IL-23) and tolerogenic (IL-10, TGF-?21, SOCS3, ALDH2 and aldefluor activity) markers were evaluated by flow cytometry or PCR. The effects of GC conditioned media on DCs were compared to exogenous retinoic acid (RA) and media collected from GC treated with N,N-diethylaminobenzaldehyde (DEAB, a potent inhibitor of ALDH). Results : DCs highly express ALDH2 that increased with both GC conditioned media and RA, and GC conditions can be be inhibited by DEAB. GC conditioned DCs showed high aldefluor activity and a tolerogenic phenotype with decreased expression of MHC class II and co-stimulatory molecules CD80 and CD86 after LPS stimulation. Conditioned media suppressed LPS stimulated expression of IL-1?2, IL-12, SOCS3 and IL-23, but stimulated ALDH2 and IL-10 expression. Conclusions : Our study demonstrates that the GC factors inhibit maturation and promote tolerogenic properties in DCs that include increased RA producing capacity. The effects of GC conditioning were similar to those seen with RA. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.