Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD, USA.
Department of Immunology, Jeonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Methods Mol Biol. 2021;2270:437-450. doi: 10.1007/978-1-0716-1237-8_23.
Regulatory B cells (Bregs) that produce IL-35 and IL-10 (i35-Bregs) regulate central nervous system (CNS) autoimmune diseases including uveitis. In the mouse model of uveitis, i35-Breg cells suppress intraocular inflammation by inducing expansion of IL-10-producing B cells (B10), IL-10-producing T cells (Tregs), and IL-35-producing T cells (iT35), suggesting that i35-Bregs orchestrate an immune-suppressive milieu that regulates immunity during autoimmune diseases. In this chapter, we discuss uveitis and therapeutic challenges that necessitate the development of cell-based therapies for the treatment of these potentially blinding diseases that cause 10% visual handicap. We then describe the methods we set up for ex vivo generation of i35-Breg cells employed in i35-Breg immunotherapy in uveitis and in other CNS autoimmune diseases.
调节性 B 细胞(Bregs)产生白细胞介素-35(IL-35)和白细胞介素-10(IL-10)(i35-Bregs)可调节中枢神经系统(CNS)自身免疫性疾病,包括葡萄膜炎。在葡萄膜炎的小鼠模型中,i35-Breg 细胞通过诱导产生白细胞介素-10 的 B 细胞(B10)、白细胞介素-10 产生的 T 细胞(Tregs)和白细胞介素-35 产生的 T 细胞(iT35)的扩张来抑制眼内炎症,这表明 i35-Bregs 协调了一个免疫抑制环境,调节自身免疫性疾病期间的免疫。在本章中,我们讨论了葡萄膜炎以及治疗方面的挑战,这些挑战需要开发基于细胞的疗法来治疗这些可能导致 10%视力障碍的致盲性疾病。然后,我们描述了我们为在葡萄膜炎和其他中枢神经系统自身免疫性疾病中进行 i35-Breg 免疫治疗而建立的体外生成 i35-Breg 细胞的方法。