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M. A. Cunningham, D.-Q. Li, L. Zhang, S. C. Pflugfelder; Epithelial-Derived Cytokines (TSLP and IL-33) May Regulate Ocular Surface Inflammation in Atopic Patients. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4867.
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Thymic stromal lymphopoietin (TSLP) is an epithelial derived pro-allergic cytokine, highly expressed at sites of allergic inflammation. Interleukin-33 (a functional ligand of the ST2 receptor) has been known to be a potential mediator of various inflammatory diseases, with ST2 playing a specific role in T-helper 2 cell differentiation. This study was to assess the expression of various cytokines, receptors, and cell membrane markers in the conjunctival tissue of patients with or without atopic disease.
Included were patients with known atopic disorders and non-atopic patients. Conjunctival epithelial RNA was obtained (from bulbar and/or tarsal conjunctiva in both eyes) and mRNA expression was determined using reverse transcription and real time PCR with TaqMan primers and probes for TSLP, IL-33, ST2, OX40, CD11c, and TSLP-receptor.
Six patients (3 atopic patients and 3 normals; 4 females, 2 males) were included in the study. The mean age in the atopic group was 26.6 years of age, and 29 years of age in the normal group. Two of the atopic patients had atopic dermatitis (involving the face), and 2/3 patients had 1-2+ upper and lower palpebral papillary reaction on slit lamp examination, without corneal involvement. Real time PCR demonstrated elevated mRNA transcripts in atopic versus normal patients of the following: TSLP (2.12±1.01 vs. 1.58±0.60, P<0.05), TSLP-receptor (5.51±2.2 vs. 1.58±0.56, P<0.05), OX40 (7.01±2.16 vs. 2.54±1.85, P<0.05), IL-33 (46.91±42.96 vs. 11.66±15.18, P<0.05), and ST2 (15.42±2.68 vs. 2.68±1.45, P<0.01). Of note, levels of CD11c (1.67 vs. 1.59), a dendritic cell marker, were similar between the two groups. Interestingly, the one atopic patient without ocular findings also demonstrated elevated mRNA expression of TSLP, TSLP-receptor, OX40, IL-33, and ST2. Furthermore, the increased expression of inflammatory mediators, TNF-α, IL-8 and MMP-9 were found in these atopic patients.
The presence of significantly elevated TSLP, OX40, IL-33 and ST2 in the conjunctiva of atopic patients suggests that epithelial-derived cytokines play a role in the regulation of ocular surface inflammation in these patients (even in the absence of ocular findings). IL-33/ST2 pathway, along with TSLP and OX40 may have direct roles in the pathogenesis of allergic ocular disease. Further studies (both animals and humans) are needed to elucidate their exact role and potential as a therapeutic target in the treatment of ocular allergic disease.
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