Frigerio Simona, Junt Tobias, Lu Bao, Gerard Craig, Zumsteg Urs, Holländer Georg A, Piali Luca
Pediatric Immunology, Department of Research and the University Children's Hospital, Basel, Switzerland.
Nat Med. 2002 Dec;8(12):1414-20. doi: 10.1038/nm1202-792. Epub 2002 Nov 4.
T cell-mediated loss of insulin-secreting beta cells in the islets of Langerhans is the hallmark of type 1 diabetes. The molecular basis for the directed migration of autoreactive T cells leading to insulitis is presently unknown. Here we demonstrate that in response to inflammation, beta cells secrete the chemokines CXC ligand 10 and CXC ligand 9, which specifically attract T-effector cells via the CXC chemokine receptor 3. In mice deficient for this receptor, the onset of type 1 diabetes is substantially delayed. Thus, in the absence of known etiological agents, CXC receptor 3 represents a novel target for therapeutic interference early in type 1 diabetes.
T细胞介导的胰岛中胰岛素分泌β细胞的丢失是1型糖尿病的标志。目前尚不清楚导致胰岛炎的自身反应性T细胞定向迁移的分子基础。在此我们证明，响应炎症时，β细胞分泌趋化因子CXC配体10和CXC配体9，它们通过CXC趋化因子受体3特异性吸引T效应细胞。在缺乏该受体的小鼠中，1型糖尿病的发病明显延迟。因此，在没有已知病原体的情况下，CXC受体3是1型糖尿病早期治疗干预的新靶点。
