Abstract
This study investigated the relationship between clinical severity and percentage of conjunctival antigen-presenting cells (APCs) in Sjögren’s syndrome (SS)-associated keratoconjunctivitis sicca (KCS). KCS clinical severity was based on symptom severity, tear volume, tear break-up time, and ocular surface dye staining. Conjunctival goblet cell density (GCD) was measured in periodic acid Schiff (PAS)-stained membranes. Conjunctival cells obtained by impression cytology were used for flow cytometry to measure percentages of CD45+HLA-DR+ APCs and mature CD11c+CD86+ dendritic cells (DCs). Compared to normal conjunctiva, the percentages of HLA-DR+ and CD11c+CD86+ cells were higher in the conjunctiva of the KCS group (p < 0.05). The percentage of CD45+HLA-DR+ cells positively correlated with clinical severity (r = 0.71, p < 0.05) and negatively correlated with GCD (r = −0.61, p < 0.05). Clinical severity also negatively correlated with GCD (r = −0.54, p < 0.05). These findings indicate that a higher percentage of APCs and mature DCs in the conjunctiva is associated with more severe KCS in SS. These APCs may contribute to the generation of the pathogenic Th1 cells that cause goblet cell loss in KCS.
Highlights
Sjögren’s syndrome (SS) causes severe aqueous-deficient dry eye and ocular surface disease, termed keratoconjunctivitis sicca (KCS) [1,2]
Goblet cell mucin has been found to mix with ovalbumin (OVA) antigen as it passes through GAPs, and immune tolerance to topically applied OVA is lost in the sterile alpha motif (SAM)-pointed domain containing (E-twenty-six) ETS transcription factor (Spdef) knockout (KO) mouse strain that lacks goblet cells [6,8]
Goblet cells could not be evaluated in samples froEmighotnceoncotrnotlrsoulbajencdtstawnod S1S1 SpSatKieCnStspabteiecnatusswe eorfepeonroorllseadm
Summary
Sjögren’s syndrome (SS) causes severe aqueous-deficient dry eye and ocular surface disease, termed keratoconjunctivitis sicca (KCS) [1,2]. Dysfunction and loss of mucin-producing conjunctival goblet cells is a key pathological feature of SS KCS [1,3]. In addition to producing mucins that lubricate and protect the ocular surface, goblet cells have been found to produce immunomodulatory factors, including retinoic acid, transforming growth factor beta 2 (TGF-β2), and mucin 2 (MUC2), which are important for maintaining immune tolerance [6,7,8,9,10]. Conjunctival goblet cells serve as passages for ocular surface antigens to antigen-presenting cells (APCs) located in the basement membrane zone and stroma [6]. Tohf ecopnujrupnocsetiovfatlhAisPCs and gosbtuledtycwelals tion iSnSv-easstisgoactieatheedrKelCatSio. nship between clinical severity and density of conjunctival APCs and goblet cells in SS-associated KCS
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