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World J Immunol. Mar 27, 2017; 7(1): 1-8
Published online Mar 27, 2017. doi: 10.5411/wji.v7.i1.1
Crucial roles of macrophages in the pathogenesis of autoimmune disease
Aya Ushio, Rieko Arakaki, Akiko Yamada, Masako Saito, Takaaki Tsunematsu, Yasusei Kudo, Naozumi Ishimaru
Aya Ushio, Rieko Arakaki, Akiko Yamada, Masako Saito, Yasusei Kudo, Naozumi Ishimaru, Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8504, Japan
Masako Saito, Department of Human Genetics, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8504, Japan
Takaaki Tsunematsu, Department of Pathology and Laboratory Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8504, Japan
Author contributions: Ushio A, Arakaki R, Yamada A, Saito M, Tsunematsu T, Kudo Y and Ishimaru N wrote a paper; Ushio A, Arakaki R, Saito M, Kudo Y and Ishimaru N prepared figures.
Supported by JSPS KAKENHI, No. JP16H02690.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naozumi Ishimaru, DDS, PhD, Department of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. ishimaru.n@tokushima-u.ac.jp
Telephone: +81-88-6337464 Fax: +81-88-6337464
Received: September 10, 2016
Peer-review started: September 11, 2016
First decision: November 14, 2016
Revised: November 18, 2016
Accepted: December 7, 2016
Article in press: December 9, 2016
Published online: March 27, 2017
Abstract

Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, naïve monocytes differentiate into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sjögren’s syndrome, to illustrate the key roles of macrophages in the cellular or molecular pathogenesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.

Keywords: Macrophage, Autoimmunity, Differentiation, Cytokines, Chemokines

Core tip: Macrophages are well known as phagocytic cells and the source of cytokines and other immunomodulators of the innate immune system. There are many reviews of macrophage function, but not many that focus on their role in autoimmunity and autoimmune disease. This review focuses on the role of tissue resident macrophages in autoimmunity both in general and several selected autoimmune diseases, develops a novel context for evaluation and a slightly different way of thinking of the complex interactions involved in “mistaken self-identity”.