Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Department of Molecular Pharmacology and Physiology, University of South Florida School of Medicine, Tampa, FL 33612, USA.
Cell Immunol. 2021 Jun;364:104360. doi: 10.1016/j.cellimm.2021.104360. Epub 2021 Apr 9.
Ig-GAD2, an antigen-specific immune modulator, requires bone marrow (BM) cell transfer in order to restore beta (β)-cell formation and induce recovery from established type 1 diabetes (T1D). The BM cells provide endothelial precursor cells (EPCs) that give rise to islet resident endothelial cells (ECs). This study shows that, during development of T1D, the immune attack causes collateral damage to the islet vascular network. The EPC-derived ECs repair and restore islet blood vessel integrity. In addition, β-cell genetic tracing indicates that the newly formed β-cells originate from residual β-cells that escaped the immune attack and, unexpectedly, from β-cell precursors. This indicates that the rejuvenated islet microenvironment invigorates formation of new β-cells not only from residual β-cells but also from precursor cells. This is twofold significant from the perspective of precursor cells as a safe reserve for restoration of β-cell mass and its promise for therapy of T1D long after diagnosis.
Ig-GAD2 是一种抗原特异性免疫调节剂，需要骨髓 (BM) 细胞转移才能恢复β (β) -细胞形成并从已建立的 1 型糖尿病 (T1D) 中恢复。BM 细胞提供内皮前体细胞 (EPC)，从而产生胰岛常驻内皮细胞 (EC)。这项研究表明，在 T1D 的发展过程中，免疫攻击会对胰岛血管网络造成附带损伤。EPC 衍生的 EC 修复并恢复胰岛血管完整性。此外，β-细胞遗传追踪表明，新形成的β细胞源自逃脱免疫攻击的残留β细胞，出乎意料的是，还源自β-细胞前体。这表明，再生的胰岛微环境不仅可以从残留的β细胞，还可以从前体细胞中激发新的β细胞形成。从前体细胞作为β细胞质量恢复的安全储备的角度来看，这具有双重意义，并且为 T1D 诊断后很长时间的治疗提供了希望。
