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

JOURNAL OF CONTROLLED RELEASE

卷:261

Article

Balmert, Stephen C.^1,2  Donahue, Cara³  Vu, John R.³  Erdos, Geza³  Falo, Louis D., Jr.^1,2,3,4,5  Little, Steven R.^1,2,6,7,8,9 

[1] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA

[3] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA

[4] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA

[5] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15260 USA

[6] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15261 USA

[7] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA

[8] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15213 USA

[9] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

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

DOI  :  10.1016/j.jconrel.2017.07.006

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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