論文

査読有り 最終著者 責任著者 国際誌
2021年4月15日

Mood Disorder in Systemic Lupus Erythematosus Induced by Antiribosomal P Protein Antibodies Associated with Decreased Serum and Brain Tryptophan

The Journal of Immunology
  • Takamasa Cho
  • ,
  • Hiroe Sato
  • ,
  • Ayako Wakamatsu
  • ,
  • Riuko Ohashi
  • ,
  • Yoichi Ajioka
  • ,
  • Toshio Uchiumi
  • ,
  • Shin Goto
  • ,
  • Ichiei Narita
  • ,
  • Yoshikatsu Kaneko

206
8
開始ページ
1729
終了ページ
1739
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4049/jimmunol.2000260
出版者・発行元
The American Association of Immunologists

Antiribosomal P protein (anti-P) autoantibodies commonly develop in patients with systemic lupus erythematosus. We have previously established hybridoma clones producing anti-P mAbs. In this study, we explored the pathogenesis of behavioral disorders induced by anti-P Abs using these mAbs. New Zealand Black × New Zealand White F1, New Zealand White, C57BL/6, and BALB/c mice were treated with 1 mg of anti-P Abs once every 2 wk. The behavioral disorder was evaluated by the tail suspension test, forced swim test, and open field test. Following administration of anti-P Abs, New Zealand Black × New Zealand White F1 and C57BL/6 mice developed depressive behavior and showed increased anxiety with elevated serum TNF-α and IL-6 levels. Anti-P Abs were not deposited in the affected brain tissue; instead, this mood disorder was associated with lower serum and brain tryptophan concentrations. Tryptophan supplementation recovered serum tryptophan levels and prevented the behavioral disorder. TNF-α and IL-6 were essential for the decreased serum tryptophan and disease development, which were ameliorated by treatment with anti-TNF-α neutralizing Abs or dexamethasone. Peritoneal macrophages from C57BL/6 mice produced TNF-α, IL-6, and IDO-1 via interaction with anti-P Abs through activating FcγRs, which were required for disease development. IVIg, which has an immunosuppressive effect partly through the regulation of FcγR expression, also prevented the decrease in serum tryptophan and disease development. Furthermore, serum tryptophan concentrations were decreased in the sera of systemic lupus erythematosus patients with anti-P Abs, and lower tryptophan levels correlated with disease activity. Our study revealed some of the molecular mechanisms of mood disorder induced by anti-P Abs.

リンク情報
DOI
https://doi.org/10.4049/jimmunol.2000260
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33789980
URL
https://syndication.highwire.org/content/doi/10.4049/jimmunol.2000260
ID情報
  • DOI : 10.4049/jimmunol.2000260
  • ISSN : 0022-1767
  • eISSN : 1550-6606
  • PubMed ID : 33789980

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