Journal
JOURNAL OF CONTROLLED RELEASE
Volume 261, Issue -, Pages 223-233Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.07.006
Keywords
Microparticles; Sustained release; Immunotherapy; Immune tolerance; Regulatory T cells; Delayed type hypersensitivity
Funding
- NIH [1-S10-OD011925- 01]
- NIHNIDCR [R01-DE021058]
- Arnold and Mabel Beckman Foundation
- Camille and Henry Dreyfus Foundation
- Wallace H. Coulter Foundation
- NIHNIAMS [R01-AR068249]
- NIHNIBIB [R01-EB012776]
- NSF Graduate Research Fellowship [DGE-1247842]
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Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin condition, characterized by an intensely pruritic rash at the site of contact with allergens like poison ivy or nickel. Current clinical treatments use topical corticosteroids, which broadly and transiently suppress inflammation and symptoms of ACD, but fail to address the underlying immune dysfunction. Here, we present an alternative therapeutic approach that teaches the immune system to tolerate contact allergens by expanding populations of naturally suppressive allergen-specific regulatory T cells (Tregs). Specifically, biodegradable poly(ethylene glycol)-poly(lactic-coglycolic acid) (PEG-PLGA) microparticles were engineered to release TGF-beta 1, Rapamycin, and IL-2, to locally sustain a microenvironment that promotes Treg differentiation. By expanding allergen-specific Tregs and reducing pro-inflammatory effector T cells, these microparticles inhibited destructive hypersensitivity responses to subsequent allergen exposure in an allergen-specific manner, effectively preventing or reversing ACD in previously sensitized mice. Ultimately, this approach to in vivo Treg induction could also enable novel therapies for transplant rejection and autoimmune diseases.
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