Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis

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.