CHU Nantes, Université de Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France; Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
CHU Nantes, Université de Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France.
Autoimmun Rev. 2021 Jun;20(6):102833. doi: 10.1016/j.autrev.2021.102833. Epub 2021 Apr 20.
Lymphocytes constitute an essential and potent effector compartment of the immune system. Therefore, their development and functions must be strictly regulated to avoid inappropriate immune responses, such as autoimmune reactions. Several lines of evidence from genetics (e.g. association with multiple sclerosis and primary biliary cirrhosis), human expression studies (e.g. increased expression in target tissues and draining lymph nodes of patients with autoimmune diseases), animal models (e.g. loss of functional protein protects animals from the development of collagen-induced arthritis, experimental autoimmune encephalomyelitis, type 1 diabetes, bleomycin-induced fibrosis) strongly support a causal link between the aberrant expression of the lymphocyte-restricted transcriptional regulator BOB.1 and the development of autoimmune diseases. In this review, we summarize the current knowledge of unusual structural and functional plasticity of BOB.1, stringent regulation of its expression, and the pivotal role that BOB.1 plays in shaping B- and T-cell responses. We discuss recent developments highlighting the significant contribution of BOB.1 to the pathogenesis of autoimmune diseases and how to leverage our knowledge to target this regulator to treat autoimmune tissue inflammation.
淋巴细胞是免疫系统中必不可少的有效效应器部分。因此，必须严格调控其发育和功能，以避免发生异常免疫反应，如自身免疫反应。遗传学方面的多项证据（如与多发性硬化症和原发性胆汁性肝硬化相关）、人类表达研究（如自身免疫性疾病患者的靶组织和引流淋巴结中表达增加）、动物模型（如功能蛋白缺失可保护动物免于发生胶原诱导性关节炎、实验性自身免疫性脑脊髓炎、1 型糖尿病、博来霉素诱导的纤维化）均强烈支持淋巴细胞特异性转录调控因子 BOB.1 的异常表达与自身免疫性疾病的发生之间存在因果关系。在这篇综述中，我们总结了 BOB.1 异常结构和功能可塑性、其表达严格调控以及 BOB.1 在塑造 B 细胞和 T 细胞反应中所起关键作用的最新知识。我们讨论了最近的研究进展，这些进展突出了 BOB.1 对自身免疫性疾病发病机制的重要贡献，以及如何利用我们的知识来靶向该调节剂以治疗自身免疫性组织炎症。
