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Allergy inhibitory receptor-1 inhibits autoantibody production via upregulation of apoptotic debris clearance by macrophages.

Authors
  • Iizuka, Akira1
  • Segawa, Seiji1
  • Kondo, Yuya1
  • Kaneko, Shunta1
  • Yokosawa, Masahiro1
  • Furuyama, Kotona1
  • Miki, Haruka1
  • Tahara-Hanaoka, Satoko2
  • Shibuya, Akira2
  • Tsuboi, Hiroto1
  • Goto, Daisuke1
  • Matsumoto, Isao1
  • Shibayama, Shiro3
  • Sumida, Takayuki1
  • 1 Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. , (Japan)
  • 2 Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. , (Japan)
  • 3 Research Center of Immunology, ONO Pharmaceutical Co. Ltd., Osaka, Japan. , (Japan)
Type
Published Article
Journal
International Journal of Rheumatic Diseases
Publisher
Wiley (Blackwell Publishing)
Publication Date
Dec 16, 2018
Identifiers
DOI: 10.1111/1756-185X.13381
PMID: 30556363
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Allergy inhibitory receptor-1 (Allergin-1) is a newly identified immune regulatory molecule thought to influence autoantibody production. Autoantibody production, like that observed in Allergin-1-deficient mice, is crucial in the pathogenesis of several autoimmune diseases such as systemic lupus erythematosus. The purpose of this study is to clarify the regulatory role of Allergin-1-mediated autoantibody production using a murine model of thymocytic anaphylaxis. C57BL/6 (WT) and Allergin-1-deficient mice were treated with apoptotic cells from naive thymocytes stimulated by dexamethasone. Antibody titers of total or immunoglobulin G (IgG) subclass of anti-double-stranded DNA (anti-dsDNA) and anti-histone antibody from serum were measured using an enzyme-linked immunosorbent assay. Macrophages from wild-type (WT) or Allergin-1-deficient mice were co-cultured with fluorescence-labeled apoptotic thymocytes or fluorogenic reagent and resultant phagocytic activity was quantified by with flow cytometry. After apoptotic cells injection, antibody titers of total and IgG3 anti-dsDNA and total anti-histone from serum were significantly increased in Allergin-1-deficient versus WT mice. Phagocytic activity was significantly lower in macrophages from Allergin-1-deficient mice versus WT mice. Allergin-1 might play an inhibitory role in autoantibody production via upregulation of macrophage phagocytosis. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

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