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Self-Antigen Expression in the Peripheral Immune System: Roles in Self-Tolerance and Type 1 Diabetes Pathogenesis

  • Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)
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Abstract

Type 1 diabetes (T1D) may result from a breakdown in peripheral tolerance that is partially controlled by the ectopic expression of peripheral tissue antigens (PTAs) in lymph nodes. Various subsets of lymph node stromal cells and certain hematopoietic cells play a role in maintaining T cell tolerance. These specialized cells have been shown to endogenously transcribe, process, and present a range of PTAs to naive T cells and mediate the clonal deletion or inactivation of autoreactive cells. During the progression of T1D, inflammation leads to reduced PTA expression in the pancreatic lymph nodes and the production of novel islet antigens that T cells are not tolerized against. These events allow for the escape and activation of autoreactive T cells and may contribute to the pathogenesis of T1D. In this review, we discuss recent findings in this area and propose possible therapies that may help reestablish self-tolerance during T1D.

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Acknowledgments

This work was supported by grants from the National Institutes of Health (NIH). Linda Yip was supported by the Juvenile Diabetes Research Foundation (JDRF) Transition Award. Work involving lymph node specimens from T1D patients was supported by the JDRF nPOD (Network for the Pancreatic Organ Donor with Diabetes). The authors wish to thank C. Garrison Fathman (Stanford University) for his useful comments and R. J. Creusot (Columbia University) for help generating the data shown in Fig. 2.

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Conflict of Interest

Rebecca Fuhlbrigge and Linda Yip declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Medicine, Division of Immunology and Rheumatology, Stanford University, 269 Campus Drive, CCSR Room 2240, Stanford, CA, 94305-5166, USA

    Rebecca Fuhlbrigge & Linda Yip

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  1. Rebecca Fuhlbrigge
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  2. Linda Yip
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Correspondence to Linda Yip.

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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes

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Fuhlbrigge, R., Yip, L. Self-Antigen Expression in the Peripheral Immune System: Roles in Self-Tolerance and Type 1 Diabetes Pathogenesis. Curr Diab Rep 14, 525 (2014). https://doi.org/10.1007/s11892-014-0525-x

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