A regulation of immune systems by T cell-metabolism and epigenetic engineering
Research aims
- Elucidation of mechanisms for metabolic and epigenetic regulation of T-cell functions
- Establishment of engineering methodology of T cell metabolism and epigenome for immune system regulation
By conducting the above topics, we will propose novel strategies for cancer immune activation, vaccine development, and treatment of allergic and autoimmune diseases.
T cells become activated by recognizing antigens and differentiate into effector cells as they clonally proliferate. After antigens are eliminated, most antigen-specific T cells die and the expanded T cells are contracted. The very limited populations of T cells remain as memory T cells, retain their acquired functions, and prepare for the antigen invasion in the future. In addition, it is known that the repeated stimulations with an antigen and the antigen-independent homeostatic proliferation could cause some T cells to acquire senescent cell-like traits and/or innate immunocompetence, affecting T cell-dependent immune responses. A failure of any of these processes can disrupt the immune system and lead to allergic disorders, autoimmune diseases, cancer, and chronic and opportunistic infections. Our laboratory aims to elucidate the regulatory mechanisms of differentiation and functions of T cells over their lifespan using “cellular metabolism” and “epigenetics” as keywords and to establish a methodology for T-cell metabolism-epigenetic engineering for regulation of immune system. As we carry out these studies and collaborate with clinical departments, medical school hospitals and medical-related companies, we hope to advocate novel strategies for cancer immune activation (application to CAR-T cells), vaccine development, and treatment of allergic and autoimmune diseases.
Masakatsu Yamashita, Ph.D.
Professor
Departments of Immunology and of Infections and Host Defenses
Ehime University Graduate School of Medicine
Members
| Immunology・Infections and host defenses | Professor | Masakatsu YAMASHITA |
|---|---|---|
| Immunology | Senior Assistant Professor | Makoto KUWAHARA |
| Senior Assistant Professor | Junpei SUZUKI | |
| Secretary | Atsuko MATSUMOTO | |
| Infections and host defenses | Senior Assistant Professor | Miyuki OMORI-MIYAKE |
| Immuno-drug chemistry | Assistant Professor | Shunsuke NOMURA |
| Translational Research Center | Assistant Professor | Yuko MATSUOKA |
Under Graduate Students/Graduate Students
| Anesthesiology | Waichi YAMAMOTO |
|---|---|
| Surgical oncology | Kenji TAKAGI |
| Anesthesiology | Taisuke HAMADA |
| Anesthesiology | Daiki TOKIWA |
| Breast Surgery | Megumi NAKAMURA |
2025
Miyuki Omori-Miyake, Ryosuke Kawakami, Makoto Kuwahara, Masataka Okabe, Jun Muto, Takeshi Imamura, Masakatsu Yamashita: Loss of Bach2 in T cells causes prolonged allergic inflammation through accumulation of effector T cells and disruption of epidermal barrier. Journal of Allergy and Clinical Immunology (2025) in press. https://doi.org/10.1016/j.jaci.2025.01.036
2024
Yuichiro Ukon, Takashi Kaito, Hiromasa Hirai, Takayuki Kitahara, Masayuki Bun, Joe Kodama, Daisuke Tateiwa, Shinichi Nakagawa, Masato Ikuta, Takuya Furuichi, Yuya Kanie, Takahito Fujimori, Shota Takenaka, Tadashi Yamamuro, Satoru Otsuru, Seiji Okada, Masakatsu Yamashita, Takeshi Imamura: Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis.Aging Cell(2024) 00:e14254. https://doi.org/10.1111/acel.14254
Waichi Yamamoto, Taisuke Hamada, Junpei Suzuki, Yuko Matsuoka,
Miyuki Omori‐Miyake, Makoto Kuwahara, Akira Matsumoto, Shunsuke Nomura, Amane Konishi, Toshihiro Yorozuya, Masakatsu Yamashita: Suppressive effect of the anesthetic propofol on the T cell function and T cell‐dependent immune responses. Scientific reports(2024) 14:19337. https://doi.org/10.1038/s41598-024-69987-z
2023
Kakuda T, Suzuki J, Matsuoka Y, Kikugawa T, Saika T, Yamashita M: Senescent CD8+ T cells acquire NK cell-like innate functions to promote antitumor immunity. Cancer Sci.(2023) 114 (7): 2810-2820 https://doi.org/10.1111/cas.15824
Noda H, Suzuki J, Matsuoka Y, Matsumoto A, Kuwahara M, Kamei Y, Takada Y, Yamashita M: The histone demethylase Utx controls CD8+ T-cell-dependent antitumor immunity via epigenetic regulation of the effector function. Cancer Sci.(2023) 114 (7): 2787-2797 https://doi.org/10.1111/cas.15814
Okamoto M*, Omori-Miyake M*, Kuwahara M, Okabe M, Eguchi M, Yamashita M: The inhibition of glycolysis in T cells by a Jak inhibitor ameliorates the pathogenesis of allergic contact dermatitis in mice. J. Invest. Dermatol.(2023) 143 (10): 1972-1982.e5 https://doi.org/10.1016/j.jid.2023.03.1667
Ikeda N, Kubota H,Suzuki R, Morita M, Yoshimura A, Osada Y, Kishida K, Kitamura D, Iwata A, Yotsumoto S, Kurotaki D, Nishimura K, Nishiyama A, Tamura T, Kamatani T, Tsunoda T, Miyako M, Asahina Y,Hayashi Y,Harada H, Harada Y, Yokota A, Hirai H, Seki T, Kuwahara M, Yamashita M, Shichino S, Tanaka M, Asano K: The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis. Cell Rep. (2023) 42 (3): 112165 https://doi.org/10.1016/j.celrep.2023.112165
Taniguchi Y, Suemori K, Tanaka K, Okamoto A, Murakami A, Miyamoto H, Takasuka Y, Yamashita M, Takenaka K: Long-term transition of antibody titers in healthcare workers following the first to fourth doses of mRNA COVID-19 vaccine: Comparison of two automated SARS-CoV-2 immunoassays. J. Infect. Chemother. (2023) 29 (5): 534-538 https://doi.org/10.1016/j.jiac.2023.01.007
2022
Suemori K , Taniguchi Y, Okamoto A , Murakami A , Ochi F , Aono H , Hato N, Osawa H, Miyamoto H, Sugiyama T ,Yamashita M, Tauchi H, Takenaka K: Two-Year Seroprevalence Surveys of SARS-CoV-2 Antibodies among Outpatients and Healthcare Workers in Ehime, Japan. Jpn. J. Infect. Dis. (2022) 75 (5): 523-526 https://doi.org/10.7883/yoken.JJID.2022.155
Choudhury ME, Mikami K, Nakanishi Y, Matsuura T, Utsunomiya R, Yano H, Kubo M, Ando R, Iwanami J, Yamashita M, Nagai M, Tanaka J: Insomnia and depressive behavior of MyD88-deficient mice: Relationships with altered microglial functions. J. Neuroimmunol. (2022) 363: 577794 https://doi.org/10.1016/j.jneuroim.2021.577794
Konishi A, Suzuki J, Kuwahara M, Matsumoto A, Nomura S, Soga T, Yorozuya T,Yamashita M: Glucocorticoid imprints a low glucose metabolism onto CD8 T cells and induces the persistent suppression of the immune response. Biochem. Biophys. Res. Commun. (2022) 588: 34-40 https://doi.org/10.1016/j.bbrc.2021.12.050
2021
Inoue T*, Omori-Miyake M*, Maruyama S, Okabe M, Kuwahara M, Honda H, Miura H, Yamashita M: The Loss of H3K27 Histone Demethylase Utx in T Cells Aggravates Allergic Contact Dermatiti. J. Immunol. (2021) 207 (9): 2223–2234 https://doi.org/10.4049/jimmunol.2001160
Tohyama M, Matsumoto A, Tsuda T, Dai X, Shiraishi K, Sayama K: Suppression of IL-17A-induced CCL20 production by cytokine inducible SH2-containing protein 1 in epidermal keratinocytes. J. Dermatol. Sci.(2021) 101 (3): 202-209 https://doi.org/10.1016/j.jdermsci.2021.01.005
