Thymic Stromal Lymphopoietin-Related Allergic Pathway in Patients With Vernal Keratoconjunctivitis.

Purpose: To investigate the expression of thymic stromal lymphopoietin (TSLP) and the relevant signaling pathways in the giant papillae obtained from patients with vernal keratoconjunctivitis (VKC) and to study the potential functional role and molecular mechanism of TSLP. Methods: Giant papillae from VKC patients and control samples were used to perform immunohistochemical staining and analyze the mRNA expression of TSLP and related pathway by real-time polymerase chain reaction. Results: TSLP was markedly expressed in the epithelial cells and some inflammatory cells of giant papillae, but not in the control conjunctival tissue. TSLP mRNA expression in the giant papillae of VKC was increased by 9.63 +/- 6 0.99 (mean +/- SD) fold compared with controls (P < 0.01). CD11c(+) and OX40L(+) immunoreactive cells largely infiltrated the giant papillae as observed by immunohistochemical staining. CD4(+)Th2 cell infiltration was observed through high immunoreactivity of CD4. Th2 cytokines (IL-4, IL-5 and IL-13) and OX40 in the VKC specimens showed increased expression. Augmented gene expression levels of CD4 (6.88 +/- 6 1.84), OX40L (7.60 +/- 1.79), OX40 (7.25 +/- 1.38), IL-4 (6.89 +/- 1.46), IL-5 (8.42 +/- 1.55), and IL-13 (9.69 +/- 1.94) were significantly different from controls (P < 0.05). Conclusions: Our observations provide strong evidence that TSLP may be a crucial factor that contributes to the development and progression of allergic conjunctivitis. The results also demonstrated that TSLP activates dendritic cells to prime CD4(+)T cells to differentiate into Th2 type and triggers Th2-dominant allergic inflammation through the TSLP/OX40L/OX40 signaling as part of immunopathogenesis of VKC.