IL-2: a promising topical treatment for Sjögren’s disease-related dry eye disease

OBJECTIVE: Dry eye disease (DED) is one of the most common features of Sjögren’s Disease (SjD) and lacks effective disease-modifying topical treatment. Previous studies have demonstrated that low-dose interleukin-2 (Ld-IL-2) exerts therapeutic effects in several autoimmune diseases by expanding regulatory T cells (Tregs) and restoring immune homeostasis. Therefore, the aim of this study was to evaluate the efficacy of Ld-IL-2 in SjD-related DED. METHODS: We administered recombinant murine IL-2 (rMuIL-2) to the ocular surface of NOD/ShiLtJGpt mice. The function of the lacrimal gland was estimated using the tear volume. Histological analysis was performed to assess corneal integrity and detect lymphocyte infiltration in the lacrimal gland. The levels of cytokines were estimated by RT-qPCR in the lacrimal functional unit (LFU) and by ELISA in serum. RESULTS: Ld-IL-2 treatment increased tear secretion by more than 50% compared with PBS controls (P = 0.0151), showing efficacy comparable to cyclosporine. Lacrimal gland inflammation was reduced, accompanied by a more than 5-fold increase in interleukin (IL)-10 (P = 0.0147) and significant suppression of interleukin (IL)-1β (P = 0.0011) and TNF(tumor necrosis factor)-α (P = 0.0416). Corneal epithelial thickness decreased significantly (P = 0.0136), with concomitant increases in IL-10 and approximately 30% reductions in IL-1β and TNF-α expression (all P < 0.05). Serum IL-17 levels showed a decreasing trend. CONCLUSION: Ld-IL-2 alleviated inflammation within the lacrimal functional unit and improved both lacrimal gland function and corneal epithelial integrity. These findings suggest that topical Ld-IL-2 may represent a potential immunomodulatory therapeutic strategy for SjD-related dry eye disease.