Research project Exploring the role of a non-coding oligonucleotide to dampen skin inflammation and itch

Skin-resident antigen-presenting cells play an important role in maintaining peripheral tolerance via immune checkpoint proteins and induction of T regulatory cells (Tregs). However, we lack knowledge on how to expand or recruit immunoregulatory cutaneous cells without causing inflammation. We have found that administration of a non-coding single-stranded oligonucleotide (ssON) leads to CCR2-dependent accumulation of CD45+CD11b+Ly6C+ cells in the skin that express substantial levels of the immunological checkpoint proteins PD-L1 and ILT3 in mice. Functionally, the cutaneous CD11b+ cells inhibited Th1/2/9 responses and promoted the induction of CD4+FoxP3+ Tregs. In addition, ssON treatment of imiquimod-induced inflammation resulted in significantly reduced Th17 responses. We have also conducted a multicenter randomized (1:1), double-blinded, placebo-controlled study in 52 client-owned dogs with mild-moderate atopic dermatitis. Treatment with the immune-modifying oligonucleotide showed significant clinical benefit over placebo with rapid onset of treatment effect, durable improvements, and a good field safety profile. Altogether, we have identified an immunomodulatory ssON that can be used therapeutically to dampen Th cells and ameliorate itch as well as induce long-term effects. Our current studies focus on revealing the immunological mechanisms governing the long-term treatment results.