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

Nature Medicine volume 8, pages 14141420 (2002) | Download Citation

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Abstract

T cell–mediated loss of insulin-secreting β 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, β 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.

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Acknowledgements

We thank H. Hengartner, R.M. Zinkernagel, E. Palmer and W. Krenger for discussions, critical review of the manuscript and the provision of RIP-GP mice; S. Hugi, E. Christen, V. Wyss and B. Odermatt for technical help; M. Török for assistance with real-time quantitative PCR; and R. Geissmann and M. Gaio for secretarial assistance.

Author information

Author notes

    • Georg A. Holländer
    •  & Luca Piali

    G.A.H and L.P. contributed equally to this study.

Affiliations

  1. Pediatric Immunology, Departments of Research and Clinical-Biological Sciences and the University Children's Hospital, Basel, Switzerland

    • Simona Frigerio
    • , Urs Zumsteg
    • , Georg A. Holländer
    •  & Luca Piali
  2. Institute for Experimental Immunology, University of Zürich, Switzerland

    • Tobias Junt
  3. Perlmutter Laboratory, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    • Bao Lu
    •  & Craig Gerard

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The authors declare no competing financial interests.

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Correspondence to Georg A. Holländer.

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DOI

https://doi.org/10.1038/nm1202-792

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