Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways.
Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways.
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DOI：
10.1007/s13346-021-01075-5
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发表时间：
2021-12
影响因子：
5.4
通讯作者：
Jewell CM
中科院分区：
文献类型：
--
作者：
Carey ST;Gammon JM;Jewell CM
自身免疫性疾病--免疫系统错误地将自身组织作为目标--仍然受到非特异性治疗的阻碍。例如，即使是分子特异性单克隆抗体也无法区分健康细胞和自反应细胞。实验性治疗方法涉及递送自身免疫靶向的自身分子，沿着免疫调节信号以产生选择性停止宿主组织攻击的调节性T细胞（Treg）。已经做了很多工作来增加使用生物材料的信号递送的效率，包括封装在聚合物微粒（MP）中以允许共递送和货物保护。然而，较少的研究比较了靶向不同TREG诱导途径的包封药物的颗粒。在本文中，我们使用聚（乳酸-乙交酯）（PLGA）共封装1型糖尿病（T1 D）相关抗原和3种不同的TREG诱导分子-雷帕霉素（Rapa），全反式维甲酸（atRA）和丁酸盐（Buty）-分别靶向Rapa（mTOR），类维生素A通路和组蛋白脱乙酰酶（HDAC）抑制的机制靶标。我们表明，所有制剂都能被抗原呈递细胞（APC）有效吸收，并且含抗原的制剂能够诱导抗原特异性T细胞增殖。此外，与抗原共负载的atRA和Rapa MP制剂降低APC活化水平，诱导TREG分化，并减少胰腺反应性T细胞中的炎性细胞因子。
Autoimmune diseases—where the immune system mistakenly targets self-tissue—remain hindered by non-specific therapies. For example, even molecularly-specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (TREG) that selectively stop attack of host tissue. Much has been done to increase the efficiency of signal delivery using biomaterials, including encapsulation in polymer microparticles (MPs) to allow for co-delivery and cargo protection. However, less research has compared particles encapsulating drugs that target different TREG inducing pathways. In this paper, we use poly (lactic-co-glycolide) (PLGA) to co-encapsulate type 1 diabetes (T1D)-relevant antigen and 3 distinct TREG-inducing molecules - rapamycin (Rapa), all-trans retinoic acid (atRA), and butyrate (Buty) – that target the mechanistic target of Rapa (mTOR), the retinoid pathway, and histone deacetylase (HDAC) inhibition, respectively. We show all formulations are effectively taken up by antigen presenting cells (APCs) and that antigen-containing formulations are able to induce proliferation in antigen-specific T cells. Further, atRA and Rapa MP formulations co-loaded with antigen decrease APC activation levels, induce TREG differentiation, and reduce inflammatory cytokines in pancreatic-reactive T cells.
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DOI：
10.4161/self.1.4.13946
发表时间：
2010-10-01
期刊：
Self/nonself
影响因子：
--
作者：
Capurso, Noah A;Look, Michael;Fahmy, Tarek M
通讯作者：
Fahmy, Tarek M
DOI：
10.1073/pnas.1105200108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Jewell, Christopher M.;Lopez, Sandra C. Bustamante;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
2.8
作者：
Juang, Jyuhn-Huarng;Van, Yang-Hau;Chang, Han-Ying
通讯作者：
Chang, Han-Ying
DOI：
10.1038/s41573-019-0041-4
发表时间：
2019-10
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Ferreira LMR;Muller YD;Bluestone JA;Tang Q
通讯作者：
Tang Q
影响因子：
6.6
作者：
Ben-Akiva E ;Est Witte S ;Meyer RA ;Rhodes KR ;Green JJ
通讯作者：
Green JJ