Treg-recruiting microspheres prevent inflammation in a murine model of dry eye disease

Michelle L. Ratay, Andrew J. Glowacki, Stephen C. Balmert, Abhinav P. Acharya, Julia Polat, Lawrence P. Andrews, Morgan V. Fedorchak, Joel S. Schuman, Dario A.A. Vignali, Steven R. Little

    Research output: Contribution to journalArticle

    Abstract

    Dry eye disease (DED) is a common ocular disorder affecting millions of individuals worldwide. The pathology of DED involves the infiltration of CD4+ lymphocytes, leading to tear film instability and destructive inflammation. In the healthy steady state, a population of immunosuppressive T-cells called regulatory T-cells (Treg) regulates proliferation of immune cells that would otherwise lead to a disruption of immunological homeostasis. For this reason, it has been suggested that Tregs could restore the immunological imbalance in DED. To this end, one possible approach would be to recruit the body's own, endogenous Tregs in order to enrich them at the site of inflammation and tissue destruction. Previously, we have demonstrated a reduction of inflammation and disease symptoms in models of periodontitis corresponding to recruitment of endogenous Tregs, which was accomplished by local placement of controlled release systems that sustain a gradient of the chemokine CCL22, referred to here as Treg-recruiting microspheres. Given that DED is characterized by a pro-inflammatory environment resulting in local tissue destruction, we hypothesized that the controlled release of CCL22 could also recruit Tregs to the ocular surface potentially mediating inflammation and symptoms of DED. Indeed, data suggest that Treg-recruiting microspheres are capable of overcoming the immunological imbalance of Tregs and CD4+ IFN-γ+ cells in the lacrimal gland. Administration of Treg-recruiting microspheres effectively mitigated the symptoms of DED as measured through a number of outcomes such as tear clearance, goblet cells density and corneal epithelial integrity, suggesting that recruitment of endogenous Treg can mitigate inflammation associated with DED.

    Original languageEnglish (US)
    Pages (from-to)208-217
    Number of pages10
    JournalJournal of Controlled Release
    Volume258
    DOIs
    StatePublished - Jul 28 2017

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    Keywords

    • CCL22
    • Drug delivery
    • Dry eye disease
    • Treg-recruiting microspheres
    • Tregs

    ASJC Scopus subject areas

    • Pharmaceutical Science

    Cite this

    Ratay, M. L., Glowacki, A. J., Balmert, S. C., Acharya, A. P., Polat, J., Andrews, L. P., Fedorchak, M. V., Schuman, J. S., Vignali, D. A. A., & Little, S. R. (2017). Treg-recruiting microspheres prevent inflammation in a murine model of dry eye disease. Journal of Controlled Release, 258, 208-217. https://doi.org/10.1016/j.jconrel.2017.05.007