☆ 4.5 Review

Epigenetic regulation of T helper cells and intestinal pathogenicity

SEMINARS IN IMMUNOPATHOLOGY (2019)

Journal

SEMINARS IN IMMUNOPATHOLOGY

Volume 41, Issue 3, Pages 379-399

Publisher

SPRINGER HEIDELBERG

DOI: 10.1007/s00281-019-00732-9

Keywords

CD4 T cell; Colitis; Mucosal immunology; Inflammatory bowel disease; Epigenetic regulation

Categories

Immunology Pathology

Funding

Japan Society for the Promotion of Science (JSPS) KAKENHI [15H02534, 17K15966]
Advanced Research and Development Programs for Medical Innovation (AMED-CREST) [16gm1010003h0001, 18gm1210001h0001]
Takeda Science Foundation
Kanae Foundation for The Promotion of Medical Science
Keio University Medical Fund
Grants-in-Aid for Scientific Research [15H02534, 17K15966] Funding Source: KAKEN

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Abstract

Inflammatory bowel diseases (IBDs) are characterized by relapsing and remitting chronic intestinal inflammation. Previous studies have demonstrated the contributions of genetic background, environmental factors (food, microbiota, use of antibiotics), and host immunity in the development of IBDs. More than 200 genes have been shown to influence IBD susceptibility, most of which are involved in immunity. The vertebrate immune system comprises a complex network of innate and adaptive immune cells that protect the host from infection and cancer. Dysregulation of the mutualistic relationship between the immune system and the gut environment results in IBD. Considering the fundamental role of epigenetic regulation in immune cells, epigenetic mechanisms, particularly in T helper (Th) cells, may play a major role in the complex regulation of mucosal immunity. Epigenetic regulation and dysregulation of Th cells are involved in the maintenance of intestinal homeostasis and its breakdown in IBD.

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Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Kazuhiko Katayama, Masumi Ai, Yoshinori Fukui, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada

Summary: A variant near the DOCK2 gene on chromosome 5 is associated with severe COVID-19 in patients under 65 years old, with this risk allele being more prevalent in East Asian individuals and rare in Europeans. Decreased expression of DOCK2 is observed in younger patients with severe cases of COVID-19, particularly in non-classical monocytes. Suppressed DOCK2 expression is also found in lung specimens from severe COVID-19 pneumonia patients. Inhibition of DOCK2 function exacerbates the severity of pneumonia in a hamster model of SARS-CoV-2 infection. These findings suggest that DOCK2 plays an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19.

NATURE (2022)

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Review Gastroenterology & Hepatology

Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis

Yohei Mikami, Junya Tsunoda, Shohei Suzuki, Ichiro Mizushima, Hiroki Kiyohara, Takanori Kanai

Summary: This article provides an overview of the use of 5-aminosalicylic acid (5-ASA) and sulfasalazine (SASP) in the treatment of ulcerative colitis, and discusses the latest insights into 5-ASA intolerance. Acute symptoms of 5-ASA intolerance syndrome include diarrhea, fever, and abdominal pain. Periodic monitoring of renal function is recommended for patients receiving 5-ASA therapy.

DIGESTION (2023)

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Article Medicine, Research & Experimental

Network Approaches to Uncover Pathogenesis and Therapeutic Targets of Inflammatory Bowel Diseases

Yohei Mikami, Takanori Kanai

Summary: Inflammatory bowel diseases (IBD) involve chronic intestinal inflammation in genetically susceptible individuals, sometimes accompanied by extraintestinal manifestations. The interplay between immune cells, local environmental factors, and intercellular networks in the gastrointestinal tract influences the molecular networks in immune cells, contributing to the complexity of IBD. Understanding the interorgan, intercellular, and intracellular networks is crucial for a comprehensive understanding of IBD.

KEIO JOURNAL OF MEDICINE (2023)

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Review Immunology

Neuroimmune crosstalk in the gut and liver

Toshiaki Teratani, Yohei Mikami, Takanori Kanai

Summary: It has long been believed that the nervous system has distinct effects on immune functions, with recent advancements deepening our understanding of the regulation of organ immune functions by the nervous system, particularly in the interaction between nerves and immune cells in vivo.

INTERNATIONAL IMMUNOLOGY (2022)

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Article Gastroenterology & Hepatology

Efficacy of Calcineurin Inhibitors for Induction of Remission in Intestinal Behcet's Disease

Takaaki Kawaguchi, Masayuki Fukata, Teppei Omori, Hiroki Kiyohara, Shinya Sugimoto, Kosaku Nanki, Tomohisa Sujino, Yohei Mikami, Takanori Kanai

Summary: This study found that calcineurin inhibitors could be a promising treatment option for refractory intestinal Behcet's disease.

CROHNS & COLITIS 360 (2022)

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Article Gastroenterology & Hepatology

Effectiveness and Durability of Ustekinumab Therapy With or Without Immunomodulators for Ulcerative Colitis Patients in Japan

Yasuhiro Aoki, Tomohisa Sujino, Takaaki Kawaguchi, Shinya Sugimoto, Fumie Shimada, Yusuke Yoshimatsu, Hiroki Kiyohara, Kosaku Nanki, Yohei Mikami, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai

Summary: The response rate of Japanese ulcerative colitis patients to ustekinumab treatment is similar to that of patients in the US and Europe. There is no significant difference between the ustekinumab monotherapy group and the ustekinumab and immunomodulator combination group in real-world settings.

CROHNS & COLITIS 360 (2022)

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Review Immunology

Vagus nerve-mediated intestinal immune regulation: therapeutic implications of inflammatory bowel diseases

Yohei Mikami, Junya Tsunoda, Hiroki Kiyohara, Nobuhito Taniki, Toshiaki Teratani, Takanori Kanai

Summary: The pathophysiology of inflammatory bowel diseases involves immunological, genetic, and environmental factors. The autonomic nervous system plays a crucial role in their development and persistence by sensing environmental stimuli. The vagus nerve has anti-inflammatory effects through the release of acetylcholine, known as the cholinergic anti-inflammatory pathway. The gut-brain axis and liver-brain-gut reflex arc regulate peripheral immune cells to maintain gut homeostasis. Targeting the neural reflex, such as via vagus nerve stimulation, is being investigated as a potential therapeutic approach for suppressing intestinal inflammation associated with IBDs.

INTERNATIONAL IMMUNOLOGY (2022)

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