IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene transfer

OBJECTIVE: Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. T(H)17 cell populations secreting IL17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL17A on SS development and onset. METHODS: Adenovirus-5 vectors expressing either IL17R:Fc fusion protein or LacZ were injected via retrograde cannulation into the salivary glands of SS-susceptible (SS(S)) C57BL/6.NOD-Aec1Aec2 mice between 6-8 weeks of age (a pre-disease stage) or 15-17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. RESULTS: Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4+IL17+ T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their ANA repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. CONCLUSIONS: The capacity of the Ad5-IL17R:Fc blocking factor to reduce SS pathology in SS(S) mice, strongly suggest that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be an effective in preventing glandular dysfunction.