Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation

Yasuhiro Katsumata, William M. Ridgway, Timothy Oriss, Xinyan Gu, David Chin, Yuehong Wu, Noreen Fertig, Tim Oury, Daniel Vandersteen, Paula Clemens, Carlos J. Camacho, Andrew Weinberg, Dana P. Ascherman

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60 Scopus citations

Abstract

Evidence implicating histidyl-tRNA synthetase (Jo-1) in the pathogenesis of the anti-synthetase syndrome includes established genetic associations linking the reproducible phenotype of muscle inflammation and interstitial lung disease with autoantibodies recognizing Jo-1. To better address the role of Jo-1-directed B and T cell responses in the context of different genetic backgrounds, we employed Jo-1 protein immunization of C57BL/6 and NOD congenic mice. Detailed analysis of early antibody responses following inoculation with human or murine Jo-1 demonstrates remarkable species-specifity, with limited cross recognition of Jo-1 from the opposite species. Complementing these results, immunization with purified peptides derived from murine Jo-1 generates B and T cells targeting species-specific epitopes contained within the amino terminal 120 amino acids of murine Jo-1. The eventual spreading of B cell epitopes that uniformly occurs 8 weeks post immunization with murine Jo-1 provides additional evidence of an immune response mediated by autoreactive, Jo-1-specific T cells. Corresponding to this self-reactivity, mice immunized with murine Jo-1 develop a striking combination of muscle and lung inflammation that replicates features of the human anti-synthetase syndrome.

Original languageEnglish (US)
Pages (from-to)174-186
Number of pages13
JournalJournal of Autoimmunity
Volume29
Issue number2-3
DOIs
StatePublished - Sep 1 2007

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Keywords

  • Animal models
  • Autoantibodies
  • Autoantigens
  • Inflammatory myopathy
  • Lung inflammation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Katsumata, Y., Ridgway, W. M., Oriss, T., Gu, X., Chin, D., Wu, Y., Fertig, N., Oury, T., Vandersteen, D., Clemens, P., Camacho, C. J., Weinberg, A., & Ascherman, D. P. (2007). Species-specific immune responses generated by histidyl-tRNA synthetase immunization are associated with muscle and lung inflammation. Journal of Autoimmunity, 29(2-3), 174-186. https://doi.org/10.1016/j.jaut.2007.07.005