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CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice

  • IMMUNOLOGY AT STANFORD UNIVERSITY
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Abstract

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing β cells in the pancreatic islets. The migration of T cells from blood vessels into pancreas is critical for the development of islet inflammation and β cell destruction in T1D. To define the roles of C–C chemokine receptor type 7 (CCR7) in recruitment of T cells into islets, we used laser capture microdissection to isolate tissue from inflamed islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young NOD mice. RT–PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19 (ELC; MIP-3β) and CCL21 (SLC) in captures from inflamed, but not from uninflamed, islets. Immunohistology studies revealed that high endothelial venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion molecule that recruits lymphocytes into islets). Desensitization of lymphocyte CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed islets, but had no effect on B cell migration into islets. These results indicate that CCR7 and its ligands are important in the recruitment of T cells into inflamed islets and thus in the pathogenesis of T1D.

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Acknowledgments

We thank Rachel Cook for critical comments on the manuscript. This work was supported by research grants from the Juvenile Diabetes Research Foundation International (JDRF 1-2001-56; to S.A.M.) and the National Institutes of Health (R01 DK06759203; to S.A.M.) and by a Digestive Disease Center grant from the National Institutes of Health (DK-56339).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305-5324, USA

    Zhongyan Shan, Baohui Xu, Anna Mikulowska-Mennis & Sara A. Michie

  2. Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China

    Zhongyan Shan

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  1. Zhongyan Shan
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Correspondence to Sara A. Michie.

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Shan, Z., Xu, B., Mikulowska-Mennis, A. et al. CCR7 directs the recruitment of T cells into inflamed pancreatic islets of nonobese diabetic (NOD) mice. Immunol Res 58, 351–357 (2014). https://doi.org/10.1007/s12026-014-8500-9

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  • DOI: https://doi.org/10.1007/s12026-014-8500-9

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