Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States.
Front Immunol. 2021 Feb 23;12:621627. doi: 10.3389/fimmu.2021.621627. eCollection 2021.
Sepsis is a life-threatening clinical syndrome that results from an overwhelming immune response to infection. During sepsis, immune cells are activated by sensing pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) through pattern recognizing receptors (PRRs). Regulation of the immune response is essential to preventing or managing sepsis. Sialic acid-binding immunoglobulin-type lectin-G (Siglec-G), a CD33 group of Siglec expressed in B-1a cells and other hematopoietic cells, plays an important immunoregulatory role. B-1a cells, a subtype of B lymphocytes, spontaneously produce natural IgM which confers protection against infection. B-1a cells also produce IL-10, GM-CSF, and IL-35 to control inflammation. Sialic acids are present on cell membranes, receptors, and glycoproteins. Siglec-G binds to the sialic acid residues on the B cell receptor (BCR) and controls BCR-mediated signal transduction, thereby maintaining homeostasis of Ca influx and NFATc1 expression. Siglec-G inhibits NF-κB activation in B-1a cells and regulates B-1a cell proliferation. In myeloid cells, Siglec-G inhibits DAMP-mediated inflammation by forming a ternary complex with DAMP and CD24. Thus, preserving Siglec-G's function could be a novel therapeutic approach in sepsis. Here, we review the immunoregulatory functions of Siglec-G in B-1a cells and myeloid cells in sepsis. A clear understanding of Siglec-G is important to developing novel therapeutics in treating sepsis.
脓毒症是一种危及生命的临床综合征，是由感染引起的免疫反应失控所致。在脓毒症中，免疫细胞通过模式识别受体（PRRs）识别病原体相关分子模式和损伤相关分子模式（DAMPs）而被激活。免疫反应的调节对于预防或管理脓毒症至关重要。唾液酸结合免疫球蛋白型凝集素-G（Siglec-G）是 CD33 组 Siglec 家族中的一员，在 B-1a 细胞和其他造血细胞中表达，发挥着重要的免疫调节作用。B-1a 细胞是 B 淋巴细胞的一个亚型，它自发产生天然 IgM，赋予其抗感染的保护作用。B-1a 细胞还产生 IL-10、GM-CSF 和 IL-35 来控制炎症。唾液酸存在于细胞膜、受体和糖蛋白上。Siglec-G 与 B 细胞受体（BCR）上的唾液酸残基结合，控制 BCR 介导的信号转导，从而维持 Ca2+内流和 NFATc1 表达的平衡。Siglec-G 抑制 B-1a 细胞中 NF-κB 的激活，并调节 B-1a 细胞的增殖。在髓样细胞中，Siglec-G 通过与 DAMPs 和 CD24 形成三元复合物来抑制 DAMPs 介导的炎症。因此，保持 Siglec-G 的功能可能是脓毒症的一种新的治疗方法。在这里，我们综述了 Siglec-G 在脓毒症中 B-1a 细胞和髓样细胞中的免疫调节功能。深入了解 Siglec-G 对于开发治疗脓毒症的新型疗法非常重要。
