Article
Immunology
Matthew D. D. Taves, Kaitlynn M. M. Donahue, Jing Bian, Margaret C. C. Cam, Jonathan D. D. Ashwell
Summary: TECs produce glucocorticoids to promote T cell repertoire, and the expression of Cyp11b1, an enzyme involved in glucocorticoid production, is dependent on Aire. Aire not only induces tissue-restricted antigen expression, but also promotes glucocorticoid production, expanding and enhancing the T cell receptor repertoire.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jason A. Carter, Leonie Stroemich, Matthew Peacey, Sarah R. Chapin, Lars Velten, Lars M. Steinmetz, Benedikt Brors, Sheena Pinto, Hannah Meyer
Summary: This study reveals the transcriptomic diversity of mTECs in the thymus and establishes a web portal for querying their transcriptome, which may aid in identifying the drivers of autoimmune diseases.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Minoru Matsumoto, Takuya Ohmura, Yuto Hanibuchi, Mayuko Ichimura-Shimizu, Yasuyo Saijo, Hirohisa Ogawa, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto, Takeshi Oya
Summary: Despite the physiological distinction between cTECs and mTECs, the origin of TCs and other thymic epithelial tumors has been unclear. By studying the mTEC-specific transcriptional regulator AIRE, it was found that a significant proportion of TCs express AIRE with characteristic nuclear dot morphology. This expression was supported by RNA-seq data and further analysis revealed that TCs exhibit molecular characteristics of multiple mTEC subpopulations, suggesting their derivation from mTECs.
Article
Immunology
Pedro Ferreirinha, Camila Ribeiro, Junko Morimoto, Jonathan J. M. Landry, Minoru Matsumoto, Catarina Meireles, Andrea J. White, Izumi Ohigashi, Leonor Araujo, Vladimir Benes, Yousuke Takahama, Graham Anderson, Mitsuru Matsumoto, Nuno L. Alves
Summary: This study identified a new classification method for the late stages of mTEC differentiation and confirmed the precursor-product relationship between different subsets through transcriptomic analysis of specific genetic programs, providing insights into their characteristics.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yoshiaki Yasumizu, Naganari Ohkura, Hisashi Murata, Makoto Kinoshita, Soichiro Funaki, Satoshi Nojima, Kansuke Kido, Masaharu Kohara, Daisuke Motooka, Daisuke Okuzaki, Shuji Suganami, Eriko Takeuchi, Yamami Nakamura, Yusuke Takeshima, Masaya Arai, Satoru Tada, Meinoshin Okumura, Eiichi Morii, Yasushi Shintani, Shimon Sakaguchi, Tatsusada Okuno, Hideki Mochizuki
Summary: This study reveals the ectopic expression of neuromuscular molecules in MG-type thymoma, specifically in a distinct subpopulation of medullary thymic epithelial cells (nmTECs). MG-thymoma exhibits microenvironments dedicated to autoantibody production and cell-cell interactions between nmTECs and T/B cells. The findings suggest that nmTECs play a significant role in the pathogenesis of MG through ectopic expression of neuromuscular molecules.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Martti Laan, Ahto Salumets, Annabel Klein, Kerli Reintamm, Rudolf Bichele, Hedi Peterson, Part Peterson
Summary: The study provides insights into the role of Aire-positive mTECs in central tolerance induction and the potential contribution of post-Aire mTECs and Hassall's corpuscles to the thymic microenvironment. The analysis suggests a novel mechanism by which late-stage mTECs in humans display a distinct pro-inflammatory signature.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Yanfei Qi, Rongchao Zhang, Yaoping Lu, Xueyang Zou, Wei Yang
Summary: The regulation of tissue-specific antigens (TSAs) and their relationship with autoimmune diseases are still under debate. This review compares the roles of Aire and Fezf2 in regulating TSAs and highlights their molecular mechanisms in autoimmune diseases, laying the foundation for improved diagnostic and therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Pedro Paranhos Tanaka, Ernna Herida Oliveira, Mayara Cristina Vieira-Machado, Max Jordan Duarte, Amanda Freire Assis, Karina Fittipaldi Bombonato-Prado, Geraldo Aleixo Passos
Summary: This study found that miR-155 may posttranscriptionally regulate Aire mRNA, reducing Aire protein levels and affecting the mRNA levels of tissue-restricted antigens. Additionally, miR-155 regulates a crucial process of chemotaxis, allowing thymocyte migration through mTECs.
Article
Biochemistry & Molecular Biology
Daniel A. Michelson, Koji Hase, Tsuneyasu Kaisho, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Lineage-defining transcription factors (TFs) for distinct cell types are present in different mTEC subtypes, and these factors are essential for the accumulation of mimetic cells and the expression of PTAs, contributing to self-tolerance.
Article
Immunology
Jiayi Dong, Lindsey M. Warner, Ling-Li Lin, Mei-Chi Chen, Ryan M. O'Connell, Li-Fan Lu
Summary: miR-155 plays a crucial role in promoting tT reg cell differentiation by promoting mTEC maturation in the thymus. RANKL stimulation induces miR-155 expression to target molecules within the TGF beta signaling pathway, safeguarding thymic medulla integrity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biology
Takahisa MIyao, Maki Miyauchi, S. Thomas Kelly, Tommy W. Terooatea, Tatsuya Ishikawa, Eugene Oh, Sotaro Hirai, Kenta Horie, Yuki Takakura, Houko Ohki, Mio Hayama, Yuya Maruyama, Takao Seki, Hiroto Ishii, Haruka Yabukami, Masaki Yoshida, Azusa Inoue, Asako Sakaue-Sawano, Atsushi Miyawaki, Masafumi Muratani, Aki Minoda, Nobuko Akiyama, Taishin Akiyama
Summary: Integrative analysis of single-cell assays revealed the existence of proliferating mTECs with specific chromatin structure in the postnatal thymus, expressing high levels of Aire and CD80. These proliferating mTECs convert into quiescent mTECs expressing high levels of TSAs after a transit amplification, suggesting the existence of transit-amplifying Aire(+)mTEC precursors during the postnatal thymic differentiation process.
Article
Multidisciplinary Sciences
Daniel A. Michelson, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) are crucial for T cell central tolerance. In addition to the transcription factor Aire, we found that mTECs express the inhibitory receptor CTLA-4. CTLA-4(+) mTECs have a distinct gene signature associated with antigen presentation and interferon-gamma signaling, complementing the role of Aire.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Hitoshi Nishijima, Minoru Matsumoto, Junko Morimoto, Kazuyoshi Hosomichi, Nobuko Akiyama, Taishin Akiyama, Takeshi Oya, Koichi Tsuneyama, Hideyuki Yoshida, Mitsuru Matsumoto
Summary: The deficiency of Aire leads to autoimmunity, and Aire indirectly induces the expression of TRAs by controlling the heterogeneity of mTECs. Analysis of transcriptomic data from Aire-augmented and Aire-deficient mTECs reveals that many Aire-dependent genes may not be direct transcriptional targets of Aire, while Ccl25 is identified as a canonical target of Aire.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Duan Ni, Jian Tan, Remy Robert, Jemma Taitz, Anjie Ge, Camille Potier-Villette, Julen Gabirel Araneta Reyes, Alanna Spiteri, Claire Wishart, Charles Mackay, Laura Piccio, Nicholas Jonathan Cole King, Laurence Macia
Summary: This study reveals a new role for GPR109A in thymic Treg development. Gpr109a-/- mice have increased Treg under basal conditions in multiple organs. GPR109A is expressed on medullary thymic epithelial cells (mTECs) and its absence leads to increased autoimmune regulator expression and enhanced mTEC functionality.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biology
Noella Lopes, Nicolas Boucherit, Jeremy C. Santamaria, Nathan Provin, Jonathan Charaix, Pierre Ferrier, Matthieu Giraud, Magali Irla
Summary: Interactions between developing T cells and Aire(+) medullary thymic epithelial cells are crucial for central tolerance induction in the thymus. Self-reactive CD4(+) thymocytes control the transcriptional regulators and composition of mTEC(lo) subsets, including Aire(+) mTEC(hi) precursors, post-Aire and tuft-like mTECs. These interactions upregulate the expression of tissue-restricted self-antigens, cytokines, chemokines, and adhesion molecules important for T-cell development. Our study reveals that self-reactive CD4(+) thymocytes control multiple facets of immature mTECs, determining their heterogeneity.
Article
Multidisciplinary Sciences
Noriaki Takemoto, Takuji Yoshimura, Satsuki Miyazaki, Fumi Tashiro, Jun-ichi Miyazaki
Article
Multidisciplinary Sciences
Satsuki Miyazaki, Fumi Tashiro, Jun-ichi Miyazaki
Article
Dentistry, Oral Surgery & Medicine
Mariko Kawai, Yo-Hei Kataoka, Junya Sonobe, Hiromitsu Yamamoto, Masakazu Inubushi, Takuya Ishimoto, Takayoshi Nakano, Hiroki Maruyama, Jun-Ichi Miyazaki, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura
JOURNAL OF PERIODONTOLOGY
(2018)
Article
Cell Biology
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-ichi Miyazaki, Michael R. Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
NATURE CELL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Takuji Yoshimura, Toshiaki Watanabe, Satomi Kuramochi-Miyagawa, Noriaki Takemoto, Yusuke Shiromoto, Akihiko Kudo, Masami Kanai-Azuma, Fumi Tashiro, Satsuki Miyazaki, Ami Katanaya, Shinichiro Chuma, Jun-ichi Miyazaki
Article
Cell Biology
Yuichi Tsuchiya, Michiko Saito, Hiroshi Kadokura, Jun-ichi Miyazaki, Fumi Tashiro, Yusuke Imagawa, Takao Iwawaki, Kenji Kohno
JOURNAL OF CELL BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Yuichiro Munakata, Tetsuya Yamada, Junta Imai, Kei Takahashi, Sohei Tsukita, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Yumiko Chiba, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Hiroyasu Hatakeyama, Makoto Kanzaki, Jun-ichi Miyazaki, Yoshitomo Oka, Hideki Katagiri
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Takumi Matsuura, Satsuki Miyazaki, Tatsushi Miyazaki, Fumi Tashiro, Jun-ichi Miyazaki
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Hung-Wei Cheng, Lucas Onder, Mario Noykovic, Charlotte Soneson, Mechthild Lutge, Natalia Pikor, Elke Scandella, Mark D. Robinson, Jun-ichi Miyazaki, Anne Tersteegen, Ursula Sorg, Klaus Pfeffer, Thomas Ruelicke, Thomas Hehlgans, Burkhard Ludewig
NATURE COMMUNICATIONS
(2019)
Article
Developmental Biology
Kenta Niimi, Misaki Kohara, Eriko Sedoh, Moe Fukumoto, Satoshi Shibata, Toshinori Sawano, Fumi Tashiro, Satsuki Miyazaki, Yoshiaki Kubota, Jun-Ichi Miyazaki, Shinobu Inagaki, Tatsuo Furuyama
Article
Medicine, Research & Experimental
Katsuhide Okunishi, Hao Wang, Maho Suzukawa, Ray Ishizaki, Eri Kobayashi, Miho Kihara, Takaya Abe, Jun-Ichi Miyazaki, Masafumi Horie, Akira Saito, Hirohisa Saito, Susumu Nakae, Tetsuro Izumi
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Satsuki Miyazaki, Fumi Tashiro, Takashi Tsuchiya, Kazuki Sasaki, Jun-ichi Miyazaki
Summary: A stable beta-cell line MIN6-CB4 was developed from a hybrid mouse model, which maintains mature beta-cell characteristics and is valuable for studying the effects of Gcg expression on beta-cell function. The study highlights the functional importance of Gcg expression and basal activation of GLP-1 receptor in beta-cells, providing an invaluable tool for investigating insulin secretion regulatory mechanisms.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Keitaro Yoshioka, Haruki Yamashita, Kazunori Shimizu, Sayako Shimomura, Takahiro Shibata, Jun-ichi Miyazaki, Hiroyuki Honda
Summary: This study identified new peptides with FFAR1 agonist activity as potential new drug candidates for treating type 2 diabetes mellitus. By utilizing phage display and physiochemical property prediction methods, peptides with high FFAR1 agonist activity can be screened. These findings provide new insights for drug development in treating type 2 diabetes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yasuki Nagai, Taka-aki Matsuoka, Naoki Shimo, Takeshi Miyatsuka, Satsuki Miyazaki, Fumi Tashiro, Jun-ichi Miyazaki, Naoto Katakami, Iichiro Shimomura
Summary: Oxidative stress is a deteriorating factor for pancreatic beta-cells under chronic hyperglycemia in diabetes. Cox6a2 plays a crucial role in beta-cell function and its deficiency leads to increased reactive oxygen species production, resulting in relative insufficiency of beta-cell function.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Peripheral Vascular Disease
Moe Fukumoto, Kanako Kondo, Kazumasa Uni, Tomoko Ishiguro, Mikiko Hayashi, Shinnosuke Ueda, Itsuki Mori, Kenta Niimi, Fumi Tashiro, Satsuki Miyazaki, Jun-Ichi Miyazaki, Shinobu Inagaki, Tatsuo Furuyama