Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward ​the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.

1型糖尿病（T1D）是一种以自身免疫性疾病为特征的胰腺β细胞破坏。T1D中有希望的治疗方法之一是胰岛的移植。但是，它有严重的局限性。为了解决这些局限性，免疫治疗策略集中在恢复免疫耐受性，防止患者自身免疫系统破坏移植细胞。巨噬细胞衍生的趋化因子，例如趋化因子配体22（CCL22）可用于调节性T细胞（Treg）募集和移植耐受。星状细胞（SCs）具有各种免疫调节功能：募集Treg和诱导T细胞凋亡。在这里，我们通过SC过度表达CCL22蛋白，在可植入的胰岛周围设计了独特的免疫特权微环境。我们准备了胰岛素分泌的小鼠胰岛素瘤6（MIN6）细胞和人类SC作为模拟幼稚的胰岛形态模型的假胰岛。我们的结果表明，转导的SC可以分泌CCL22并将Treg募集到植入位点体内。这项研究有望为SC-胰岛的相互作用以及配体的合成和从SCs在移植部位的转运提供基本的了解，以确保局部免疫耐受。我们的结果还建立了一个新的范例，可以为其他慢性疾病（例如糖尿病，贫血和中枢神经系统（CNS）疾病）创建可耐受的移植物，并提高了移植物耐受性的科学水平。