Volume 21, Issue 12 p. 2071-2078
ORIGINAL ARTICLE

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

Akira Iizuka

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Seiji Segawa

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Yuya Kondo

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Shunta Kaneko

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Masahiro Yokosawa

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Kotona Furuyama

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Haruka Miki

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Satoko Tahara‐Hanaoka

Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Akira Shibuya

Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Hiroto Tsuboi

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Daisuke Goto

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Isao Matsumoto

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

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Shiro Shibayama

Research Center of Immunology, ONO Pharmaceutical Co. Ltd., Osaka, Japan

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Takayuki Sumida

Corresponding Author

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Correspondence

Takayuki Sumida, Division of Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Email: tsumida@md.tsukuba.ac.jp

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First published: 16 December 2018

Abstract

Aim

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.

Methods

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.

Results

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.

Conclusion

Allergin‐1 might play an inhibitory role in autoantibody production via upregulation of macrophage phagocytosis.

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