Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Department of Immunology, Mayo Clinic, Rochester, MN 55905
J Immunol. 2020 Jun 15;204(12):3071-3076. doi: 10.4049/jimmunol.2000023. Epub 2020 Apr 29.
The immune system contains a series of checks and balances that maintain tolerance and prevent autoimmunity. Sialic acid-binding Ig-type lectins (Siglecs) are cell surface receptors found on immune cells and inhibit inflammation by recruiting protein tyrosine phosphatases to ITIMs. Islet-resident macrophages express Siglec-E, and Siglec-E expression decreases on islet-resident macrophages as insulitis progresses in the NOD mouse. The sialyltransferase ST8Sia6 generates α-2,8-disialic acids that are ligands for Siglec-E in vivo. We hypothesized that engaging Siglec-E through ST8Sia6-generated ligands may inhibit the development of immune-mediated diabetes. Constitutive overexpression of ST8Sia6 in pancreatic β cells mitigated hyperglycemia in the multiple low-dose streptozotocin model of diabetes, demonstrating that engagement of this immune receptor facilitates tolerance in the setting of inflammation and autoimmune disease.
免疫系统包含一系列的检查和平衡机制，以维持耐受和防止自身免疫。唾液酸结合免疫球蛋白型凝集素（Siglecs）是免疫细胞表面的受体，通过招募蛋白酪氨酸磷酸酶到 ITIM 来抑制炎症。胰岛固有巨噬细胞表达 Siglec-E，并且随着 NOD 小鼠胰岛炎的进展，胰岛固有巨噬细胞上的 Siglec-E 表达减少。唾液酸转移酶 ST8Sia6 产生α-2,8-二唾液酸，这些是体内 Siglec-E 的配体。我们假设通过 ST8Sia6 产生的配体与 Siglec-E 结合可能会抑制免疫介导的糖尿病的发展。在链脲佐菌素多次低剂量模型的糖尿病中，胰腺β细胞中 ST8Sia6 的组成型过表达减轻了高血糖，表明在炎症和自身免疫性疾病的情况下，这种免疫受体的结合促进了耐受。
