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.
Frigerio
Simona
S
Pediatric Immunology, Department of Research and the University Children's Hospital, Basel, Switzerland.
Junt
Tobias
T
Lu
Bao
B
Gerard
Craig
C
Zumsteg
Urs
U
Holländer
Georg A
GA
Piali
Luca
L
D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine