Core B

核心B -总结/摘要 核心B将提供用于体内施用的抗体包被的纳米颗粒（NP）和FRC，以重新编程细胞。 LN微环境的调节环境，促进移植耐受。这些策略 代表了只有这里的团队提出的尖端方法，因此， 代表着与传统的诱导耐受性的方法的根本背离。这些技术提供了 核心B为开发第一类旨在重新编程 LN的微环境。除了将这些数据应用于移植之外，它们还可以具有 在LN在发病机制中起中心作用的其它免疫病症中的主要影响（例如， 自身免疫性疾病和肿瘤免疫）。这个核心将充分表征和合成大量的 抗层粘连蛋白α5（LAMA 5）和抗CD 40 L mAb的MECA-79结合载体（项目2 - Bromberg），作为 以及衰老清除剂（SA）（项目1- Abdi）。核心B还将合成掺入染料的NP（包括 红外染料），以核实贩运到LNs以及控制批次的质量。这将是第一 该平台靶向LN用于药物递送，以将其微环境重新编程为免疫耐受。在 此外，核心B将扩增从健康小鼠的LN分离的FRC，并将完全表征 FRC特异性标志物。这些细胞将提供给项目1进行实验，评估它们对 下调LN纤维化及其对移植耐受的有害作用。 核心B的具体目标如下： 目标1。为了表征和提供抗体缀合的NP，用于靶向递送免疫递送。 治疗LN以促进移植耐受性。 目标二。表征并提供健康的FRC用于体内给药，以促进移植 通过重新编程LN微环境的耐受性。

CORE B - SUMMARY/ABSTRACT Core B will provide antibody-coated nanoparticles (NPs) and FRCs for in vivo administration to reprogram the LN microenvironment towards a regulatory milieu that promotes transplant tolerance. These strategies represent cutting-edge approaches which have been set forth only by the teams here, and hence they represent a radical departure from the traditional approaches to induce tolerance. These techniques provided by Core B lay the groundwork for developing first class of therapeutics aimed towards reprogramming the microenvironment of the LN. In addition to the applications of these data to transplantation, they can also have a major impact in other immune conditions in which the LN plays a central role in the pathogenesis (e.g., autoimmune diseases and tumor immunity). This Core will fully characterize and synthesize large quantities of MECA-79-conjugated carriers of anti-laminin α5 (LAMA5) and anti-CD40L mAbs (Project 2 - Bromberg), as well as senolytic agents (SAs) (Project 1- Abdi). Core B will also synthesize dye-incorporating NPs (including infrared dye) to verify trafficking to LNs as well as to control the quality of the batches. This will be the first platform that targets LNs for drug delivery to reprogram their microenvironment towards immune tolerance. In addition, Core B will expand FRCs isolated from the LNs of healthy mice and will be fully characterized for FRC-specific markers. These cells will be provided to Project 1 for experiments that assess their impact on downregulating LN fibrosis and its deleterious effects on transplant tolerance. The specific aims of Core B are as follows: Aim 1. To characterize and provide antibody-conjugated NPs for targeted delivery of immune therapeutics to the LN to promote transplant tolerance. Aim 2. To characterize and provide healthy FRCs for in vivo administration to promote transplant tolerance by reprogramming the LN microenvironment.