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IL-17 Contributes to the Development of Chronic Rejection in a Murine Heart Transplant Model

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Abstract

Background

Although interleukin-17 (IL-17) has been reported to participate in the pathogenesis of infectious, autoimmune and allergic disorders, the precise role in allograft rejection remains uncertain. This study illustrates that IL-17 contributes to the pathogenesis of chronic allograft rejection.

Result

Utilizing a murine heterotopic heart transplant model system, IL-17-deficient recipient mice had decreased allograft inflammatory cell recruitment, decreased IL-6, MCP-1, and KC production, and reduced graft coronary artery disease (GCAD). Intragraft gamma delta (γδ) T cells appear to be the predominant source of IL-17 production.

Conclusion

Therefore, IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

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Acknowledgments

This work was supported by funds from the Falk Research Fund, Department of Cardiothoracic Surgery at Stanford University Medical School, American Association for Thoracic Surgery (Norman E. Shumway award to MPF), National Institute of Biomedical Innovation (ID 05-24; H.S.), Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (20790700: N.K.), and Program for Improvement of Research Environment for Young Researchers, The Special Coordination Funds for Promoting Science and Technology of MEXT (S.N.). The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Dr., CVRB MC 5407, Stanford, CA, 94305, USA

    Satoshi Itoh, Jeffrey B. Velotta, Naoyuki Kimura, Robert C. Robbins & Michael P. Fischbein

  2. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan

    Susumu Nakae, Naoki Kajiwara & Hirohisa Saito

  3. Atopy Research Center, Juntendo University, Tokyo, 113-8421, Japan

    Susumu Nakae, Naoki Kajiwara & Hirohisa Saito

  4. Frontier Research Initiative, The Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Susumu Nakae

  5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Robert C. Axtell & Lawrence Steinman

  6. Center for Experimental Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Yoichiro Iwakura

  7. Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama, 330-0834, Japan

    Satoshi Itoh & Hideo Adachi

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  1. Satoshi Itoh
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  2. Susumu Nakae
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  7. Yoichiro Iwakura
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  9. Hideo Adachi
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  10. Lawrence Steinman
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  12. Michael P. Fischbein
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Corresponding author

Correspondence to Michael P. Fischbein.

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Itoh, S., Nakae, S., Axtell, R.C. et al. IL-17 Contributes to the Development of Chronic Rejection in a Murine Heart Transplant Model. J Clin Immunol 30, 235–240 (2010). https://doi.org/10.1007/s10875-009-9366-9

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  • DOI: https://doi.org/10.1007/s10875-009-9366-9

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