In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis.
In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis.
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DOI：
10.1016/j.jconrel.2017.07.006
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发表时间：
2017-09-10
影响因子：
10.8
通讯作者：
Little, Steven R.
中科院分区：
文献类型：
--
作者：
Balmert, Stephen C.;Donahue, Cara;Vu, John R.;Erdos, Geza;Falo, Louis D., Jr.;Little, Steven R.
关键词：
过敏性接触性皮炎（ACD）是一种常见的T细胞介导的炎症性皮肤病，其特征是在与毒葛或镍等过敏原接触的部位出现强烈的皮疹。目前的临床治疗使用局部皮质类固醇，其广泛且短暂地抑制炎症和ACD症状，但未能解决潜在的免疫功能障碍。在这里，我们提出了一种替代的治疗方法，教导免疫系统通过扩大自然抑制性过敏原特异性调节性T细胞（T细胞）的群体来耐受接触性过敏原。具体而言，可生物降解的聚（乙二醇）-聚（乳酸-共-乙醇酸）（PEG-PLGA）微粒被工程化以释放TGF-β1、雷帕霉素和IL-2，以局部维持促进Treg分化的微环境。通过扩增过敏原特异性T细胞和减少促炎效应T细胞，这些微粒以过敏原特异性方式抑制对随后过敏原暴露的破坏性超敏反应，有效预防或逆转先前致敏小鼠的ACD。最终，这种体内Treg诱导的方法也可以实现移植排斥和自身免疫性疾病的新疗法。
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.
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DOI：
10.1016/j.jconrel.2008.10.011
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Jhunjhunwala S;Raimondi G;Thomson AW;Little SR
通讯作者：
Little SR
影响因子：
6.2
作者：
Koehl, GE;Andrassy, J;Geissler, EK
通讯作者：
Geissler, EK
DOI：
10.1073/pnas.0909384107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Letourneau, Sven;van Leeuwen, Ester M. M.;Boyman, Onur
通讯作者：
Boyman, Onur
影响因子：
64.8
作者：
Clemente-Casares, Xavier;Blanco, Jesus;Santamaria, Pere
通讯作者：
Santamaria, Pere
影响因子：
6.5
作者：
Lehtimaki, Sari;Savinko, Terhi;Fyhrquist, Nanna
通讯作者：
Fyhrquist, Nanna