Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Mol Aspects Med. 2023 Apr;90:101140. doi: 10.1016/j.mam.2022.101140. Epub 2022 Aug 30.
Autoimmune diseases affect tens of millions of people just in the United States alone. Most of the available treatment options are aimed at reducing symptoms but do not lead to cures. Individuals affected with autoimmune diseases suffer from the imbalance between tolerogenic and immunogenic functions of their immune system. Often pathogenesis is mediated by autoreactive B and T cells that escape central tolerance and react against self-antigens attacking healthy tissues in the body. In recent years Siglecs, sialic-acid-binding immunoglobulin (Ig)-like lectins, have gained attention as immune checkpoints for therapeutic interventions to dampen excessive immune responses and to restore immune tolerance in autoimmune diseases. Many Siglecs function as inhibitory receptors suppressing activation signals in various immune cells through binding to sialic acid ligands as signatures of self. In this review, we highlight potential of Siglecs in suppressing immune responses causing autoimmune diseases. In particular, we cover the roles of CD22 and Siglec-G/Siglec-10 in regulating autoreactive B cell responses. We discuss several functions of Siglec-10 in the immune modulation of other immune cells, and the potential of therapeutic strategies for restoring immune tolerance by targeting Siglecs and expanding regulatory T cells. Finally, we briefly review efforts evaluating Siglec-based biomarkers to monitor autoimmune diseases.
自身免疫性疾病仅在美国就影响了数千万人。大多数可用的治疗选择旨在减轻症状，但不能治愈疾病。患有自身免疫性疾病的个体患有免疫系统的耐受性和免疫原性功能之间的失衡。发病机制通常由自身反应性 B 和 T 细胞介导，这些细胞逃避中枢耐受并针对攻击体内健康组织的自身抗原发生反应。近年来，唾液酸结合免疫球蛋白（Ig）样凝集素 Siglecs 作为治疗干预的免疫检查点引起了人们的关注，以抑制过度的免疫反应并恢复自身免疫性疾病中的免疫耐受。许多 Siglecs 作为抑制性受体发挥作用，通过与作为自身标志的唾液酸配体结合，抑制各种免疫细胞中的激活信号。在这篇综述中，我们强调了 Siglecs 在抑制引起自身免疫性疾病的免疫反应方面的潜力。特别是，我们介绍了 CD22 和 Siglec-G/Siglec-10 在调节自身反应性 B 细胞反应中的作用。我们讨论了 Siglec-10 在调节其他免疫细胞免疫中的几种功能，以及通过靶向 Siglecs 和扩增调节性 T 细胞来恢复免疫耐受的治疗策略的潜力。最后，我们简要回顾了评估基于 Siglec 的生物标志物来监测自身免疫性疾病的努力。
