Dispensable Role of Aire in CD11c+ Conventional Dendritic Cells for Antigen Presentation and Shaping the Transcriptome

Author:

Miyazawa Ryuichiro1ORCID,Nagao Jun-ichi23,Arita-Morioka Ken-ichi2,Matsumoto Minoru14ORCID,Morimoto Junko1,Yoshida Masaki5,Oya Takeshi4,Tsuneyama Koichi6ORCID,Yoshida Hideyuki5,Tanaka Yoshihiko23ORCID,Matsumoto Mitsuru1ORCID

Affiliation:

1. *Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan;

2. †Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, Sawara-ku, Fukuoka, Japan;

3. ‡Oral Medicine Research Center, Fukuoka Dental College, Sawara-ku, Fukuoka, Japan;

4. §Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;

5. ¶YCI Laboratory for Immunological Transcriptomics, RIKEN Center for Integrative Medical Science, Yokohama, Japan; and

6. ‖Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

Abstract

Abstract Aire, the defect of which is responsible for the development of autoimmunity, is predominantly expressed in medullary thymic epithelial cells, and it controls a wide variety of genes, including those of tissue-restricted Ags, for establishing thymic tolerance. Aire is also expressed from APCs in the periphery, called extrathymic Aire-expressing cells (eTACs), and their complementing role to thymic tolerance has been suggested. eTACs are composed of two distinct classes of APCs, conventional dendritic cell (cDC)–type and group 3 innate lymphoid cell (ILC3)-like–type expressing retinoic acid receptor–related orphan receptor γt (RORγt). Although the essential role of Aire in the latter in the Th17-mediated immune response against Candida albicans has been reported, the role of Aire in the cDC-type eTACs for this action has not been examined. Furthermore, the significance of Aire in the production of the transcriptome of the cDC-type eTACs remains unknown. We have approached these issues using a high-fidelity Aire-reporter mouse strain. We found that although the cDC-type eTACs dominated ILC3-like–type eTACs in number and they served as efficient APCs for the immune response against an exogenous Ag as well as for the C. albicans–specific Th17 immune response, loss of Aire in cDC-type eTACs showed no clear effect on these functions. Furthermore, loss of Aire showed no major impact on the transcriptome from cDC-type eTACs. These results suggested that Aire in cDC-type eTACs may not have a cell-intrinsic role in the immune response in contrast to the role of Aire in ILC3-like–type eTACs.

Publisher

The American Association of Immunologists

Subject

Immunology and Allergy,General Medicine,Immunology

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Aire in Autoimmunity;Annual Review of Immunology;2024-06-28

2. Extrathymic AIRE-Expressing Cells: A Historical Perspective;Advances in Experimental Medicine and Biology;2024

3. Learning the Autoimmune Pathogenesis Through the Study of Aire;Advances in Experimental Medicine and Biology;2024

4. Revisiting Aire and tissue-restricted antigens at single-cell resolution;Frontiers in Immunology;2023-05-03

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