Ratay Michelle L, Glowacki Andrew J, Balmert Stephen C, Acharya Abhinav P, Polat Julia, Andrews Lawrence P, Fedorchak Morgan V, Schuman Joel S, Vignali Dario A A, Little Steven R
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15216, United States.
Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15216, United States.
J Control Release. 2017 Jul 28;258:208-217. doi: 10.1016/j.jconrel.2017.05.007. Epub 2017 May 10.
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.
干眼症（DED）是一种常见的眼部疾病，影响着全球数百万人。DED的病理过程涉及CD4淋巴细胞浸润，导致泪膜不稳定和破坏性炎症。在健康的稳态下，一类称为调节性T细胞（Treg）的免疫抑制性T细胞群体调节免疫细胞的增殖，否则会导致免疫稳态的破坏。因此，有人提出Treg可以恢复DED中的免疫失衡。为此，一种可能的方法是募集机体自身的内源性Treg，以便在炎症和组织破坏部位富集它们。此前，我们已经证明，在牙周炎模型中，通过局部放置维持趋化因子CCL22梯度的控释系统（在此称为Treg募集微球）来募集内源性Treg，可减轻炎症和疾病症状。鉴于DED的特征是促炎环境导致局部组织破坏，我们假设CCL22的控释也可以将Treg募集到眼表，可能介导DED的炎症和症状。事实上，数据表明，Treg募集微球能够克服泪腺中Treg和CD4 IFN-γ细胞的免疫失衡。通过泪液清除、杯状细胞密度和角膜上皮完整性等多项指标测量，给予Treg募集微球可有效减轻DED的症状，这表明募集内源性Treg可以减轻与DED相关的炎症。
