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J Control Release. 2017 Sep 10;261:223-233. doi: 10.1016/j.jconrel.2017.07.006. Epub 2017 Jul 8.

In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis.

Author information

1
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, United States.
2
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
3
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, United States; Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, United States; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, United States; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address: lof2@pitt.edu.
4
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, United States; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261, United States; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, United States. Electronic address: srlittle@pitt.edu.

Abstract

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-co-glycolic acid) (PEG-PLGA) microparticles were engineered to release TGF-β1, 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.

KEYWORDS:

Delayed type hypersensitivity; Immune tolerance; Immunotherapy; Microparticles; Regulatory T cells; Sustained release

PMID:
28694031
DOI:
10.1016/j.jconrel.2017.07.006
[Indexed for MEDLINE]

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