دورية أكاديمية
Treg-recruiting microspheres prevent inflammation in a murine model of dry eye disease.
العنوان: | Treg-recruiting microspheres prevent inflammation in a murine model of dry eye disease. |
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المؤلفون: | Ratay ML; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15216, United States., Glowacki AJ; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15216, United States., Balmert SC; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15216, United States., Acharya AP; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15216, United States., Polat J; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States., Andrews LP; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States., Fedorchak MV; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15216, United States; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States., Schuman JS; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States., Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States; Department of Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, United States., Little SR; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15216, United States; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15216, United States; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States. Electronic address: srlittle@pitt.edu. |
المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Jul 28; Vol. 258, pp. 208-217. Date of Electronic Publication: 2017 May 10. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
مواضيع طبية MeSH: | Anti-Inflammatory Agents/*administration & dosage , Chemokine CCL22/*administration & dosage , Delayed-Action Preparations/*chemistry , Dry Eye Syndromes/*complications , Inflammation/*prevention & control , T-Lymphocytes, Regulatory/*drug effects, Animals ; Anti-Inflammatory Agents/therapeutic use ; Chemokine CCL22/therapeutic use ; Disease Models, Animal ; Drug Delivery Systems ; Dry Eye Syndromes/immunology ; Female ; Inflammation/immunology ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory/immunology |
مستخلص: | 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. (Copyright © 2017. Published by Elsevier B.V.) |
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معلومات مُعتمدة: | TL1 TR000145 United States TR NCATS NIH HHS; TL1 TR001858 United States TR NCATS NIH HHS; R01 DK089125 United States DK NIDDK NIH HHS; P01 AI108545 United States AI NIAID NIH HHS; P30 EY008098 United States EY NEI NIH HHS |
فهرسة مساهمة: | Keywords: CCL22; Drug delivery; Dry eye disease; Treg-recruiting microspheres; Tregs |
المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0 (Chemokine CCL22) 0 (Delayed-Action Preparations) |
تواريخ الأحداث: | Date Created: 20170515 Date Completed: 20180329 Latest Revision: 20231110 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7805562 |
DOI: | 10.1016/j.jconrel.2017.05.007 |
PMID: | 28501670 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-4995 |
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DOI: | 10.1016/j.jconrel.2017.05.007 |