免疫恒常性研究チーム

Takakura Y, Machida M, Terada N, Katsumi Y, Kawamura S, Horie K, Miyauchi M, Ishikawa T, Akiyama N, Seki T, Miyao T, Hayama M, Endo R, Ishii H, Maruyama Y, Hagiwara N, Kobayashi TJ, Yamaguchi N, Takano H, Akiyama T, Yamaguchi N.

Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity

Nat Commun. 15(1):953 (2024) プレスリリース

 

Horie K, Namiki K, Kinoshita K, Miyauchi M, Ishikawa T, Hayama M, Maruyama Y, Hagiwara N, Miyao T, Murata S, Kobayashi TJ, Akiyama N, Akiyama T

Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells

Front Immunol.  14:1186154 (2023) 

 

Ishikawa T, Horie K, Takakura Y, Ohki H, Maruyama Y, Hayama M, Miyauchi M, Miyao T, Hagiwara N, Kobayashi TJ, Akiyama N, Akiyama T

T-cell receptor repertoire analysis of CD4-positive T cells from blood and an affected organ in an autoimmune mouse model

Genes Cells. 12:929-941 (2023) 

 

Ishikawa T, Ishii H, Miyao T, Horie K, Miyauchi M, Akiyama N, Akiyama T

Sample Preparation and Integrative Data Analysis of a Droplet-based Single-Cell ATAC-sequencing Using Murine Thymic Epithelial Cells

Bio Protoc. 13:e4588 (2023)

 

Katayama Y, Yokota R, Akiyama T, Kobayashi TJ.

Machine Learning Approaches to TCR Repertoire Analysis

Front Immunol.  13:858057 (2022)

 

Miyao T, Miyauchi M, Kelly ST, Terooatea TW, Ishikawa T, Oh E, Hirai S, Horie K, Takakura Y, Ohki H, Hayama M, Maruyama Y, Seki T, Ishii H,Yabukami H, Yoshida M, Inoue A, Sakaue-Sawano A, Miyawaki A, Muratani M, Minoda A, Akiyama N, Akiyama T.

Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator.

Elife  11: e73998 (2022) プレスリリース

 

Nishijima H, Matsumoto M, Morimoto J, Hosomichi K, Akiyama N, Akiyama T, Oya T, Tsuneyama K, Yoshida H, Matsumoto M*.

Aire Controls Heterogeneity of Medullary Thymic Epithelial Cells for the Expression of Self-Antigens

J. Immunol.  208:303-320 (2022)　

 

Fujimori A, Hirakawa H, Liu C, Akiyama T, Engelward BP, Nickoloff JA, Suzuki M, Wang B, Nenoi M, Sai S.

Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma.

Am J Cancer Res  12:562-567 (2022)

 

Akiyama T*, Suzuki T, Yamamoto T.

RNA decay machinery safeguards immune cell development and immunological responses

Trends Immunol.  42:447-460 (2021)

 

Akiyama T*,  Yamamoto T.

Regulation of Early Lymphocyte Development via mRNA Decay Catalyzed by the CCR4-NOT Complex

Front. Immunol   12:715675 (2021)

 

Yamamoto M, Gohda J, Akiyama T, Inoue JI*.

TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation

Proc Jpn Acad Ser B Phys Biol Sci. 97:145-160 (2021)

 

Ishikawa T, Akiyama N,  & Akiyama T* 

In Pursuit of Adult Progenitors of Thymic Epithelial Cells.

Front. Immunol 12:621824 (2021) 

 

Ito-Kureha T, Miyao T, Nishijima S, Suzuki T, Koizumi S, Villar-Briones A, Takahashi A, Akiyama N, Morita M, Naguro I, Ishikawa H, Ichijo H, Akiyama T* & Yamamoto T*

The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression

Nat. Commun. 11:6169 (2020) プレスリリース

 

Akiyama T*, Horie K, Hinoi E, Hiraiwa M, Kato A, Maekawa Y, Takahashi A, Furukawa S.

NPJ Microgravity. 6:14 (2020)

 

Nakamura T, Hashikawa C, Okabe K, Yokote Y, Chirifu M, Toma-Fukai S, Nakamura N, Matsuo M, Kamikariya M, Okamoto Y, Gohda J, Akiyama T, Semba K, Ikemizu S, Otsuka M, Inoue JI, Yamagata Y*.

Sci Rep. 10: 5152 (2020)

 

Horie K, Kato T, Kudo T, Sasanuma H, Miyauchi M, Akiyama N, Miyao T, Seki T, Ishikawa T, Takakura Y, Shirakawa M, Shiba D, Hamada M, Jeon H, Yoshida N, Inoue JI, Muratani M, Takahashi S, Ohno H*, and Akiyama T*.

Impact of spaceflight on the murine thymus and mitigation by exposure to artificial gravity during spaceflight.

Sci Rep. 9: 19866 (2019) プレスリリース

 

Kaneko KB, Tateishi R, Miyao T, Takakura Y, Akiyama N, Yokota R, Akiyama T* and Kobayashi TJ*.

Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice.

Commun Biol. 2: 444 (2019) プレスリリース

 

Yamamoto M, Abe C, Wakinaga S, Sakane K, Yumiketa Y, Taguchi Y, Matsumura T, Ishikawa K, Fujimoto J, Semba K, Miyauchi M, Akiyama T, and Inoue JI.

TRAF6 maintains mammary stem cells and promotes pregnancy-induced mammary epithelial cell expansion.

Commun Biol. 2: 292 (2019)

 

Horie K, Sasanuma H, Kudo T, Fujita SI, Miyauchi M, Miyao T, Seki T, Akiyama N, Takakura Y, Shimbo M, Jeon H, Shirakawa M, Shiba D, Yoshida N, Muratani M, Takahashi S, and Akiyama T*

 

Horie K, Kudo T, Yoshinaga R, Akiyama N, Sasanuma H, Kobayashi TJ, Shimbo M, Jeon H, Miyao T, Miyauchi M, Shirakawa M, Shiba D, Yoshida N, Muratani M, Takahashi S, and Akiyama T*.

Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire).

Biochem. Biophys. Res. Commun. 501: 745-750 (2018)

 

Kanaya T, Sakakibara S, Jinnohara T, Hachisuka M, Tachibana N, Hidano S, Kobayashi T, Kimura S, Iwanaga T, Nakagawa T, Katsuno T, Kato N, Akiyama T, Sato T, Williams IR, Ohno H.

Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.

J. Exp. Med. 215: 501-519 (2018).

 

Inuki S, Aiba T, Kawakami S, Akiyama T, Inoue JI, Fujimoto Y.

Chemical Synthesis of d-glycero-d-manno-Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation.

Org Lett. 19: 3079-3082 (2017)

 

Akiyama N, Takizawa N, Miyauchi M, Yanai H, Tateishi R, Shinzawa M, Yoshinaga R, Kurihara M, Demizu Y, Yasuda H, Yagi S, Wu G, Matsumoto M, Sakamoto R, Yoshida N, Penninger JM., Kobayashi Y, Inoue J, and Akiyama T*.

Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator

J. Exp. Med. 213: 1441-1458 (2016)

 

Kawasaki M, Kawasaki K, Oommen S, Blackburn J, Watanabe M, Nagai T, Kitamura A, Maeda T, Liu B, Schmidt-Ullrich R, Akiyama T, Inoue J, Hammond NL, Sharpe PT, Ohazama A,

Regional regulation of filiform tongue papillae development by Ikkα/Irf6

Dev Dyn, 245: 937-946 (2016).

 

Shimbo M, Kudo T, Hamada M, Jeon H, Imamura Y, Asano K, Okada R, Tsunakawa Y, Mizuno S, Yagami KI, Ishikawa C, Li H, Shiga T, Ishida J, Hamada J, Murata K, Ishimaru T, Hashimoto M, Fukamizu A, Yamane M, Ikawa M, Morita H, Shinohara M, Asahara H, Akiyama T, Akiyama N, Sasanuma H, Yoshida N, Zhou R, Wang YY, Ito T, Kokubu Y, Noguchi TK, Ishimine H, Kurisaki A, Shiba D, Mizuno H, Shirakawa M, Ito N, Takeda S, Takahashi S.

Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

Exp Anim. 65: 175-187 (2016).

 

Tateishi R, Akiyama N, Miyauchi M, Yoshinaga R, Sasanuma H, Kudo T, Shimbo M, Shinohara M, Obata K, Inoue J, Shirakawa M, Shiba D, Asahara H, Yoshida N, Takahashi S, Morita H, and Akiyama T*.

Hypergravity provokes a temporary reduction in CD4⁺CD8⁺ thymocyte number and a persistent decrease in medullary thymic epithelial cell frequency in mice.

Plos one., 10: e0141650 (2015)

 

Varney M, Niederkorn M, Konno H, Matsumura T, Gohda J, Yoshida N, Akiyama T, Christie S, Fang J, Miller D, Jerez A, Karsan A, Maciejewski J, Meetei M, Inoue J, and Starczynowski D.

Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor/TRAF6 signaling.

J. Exp. Med., 212: 1967-1985 (2015)

 

Seki T, Yamamoto M, Taguchi Y, Miyauchi M, Akiyama N, Yamaguchi N, Gohda J, Akiyama T, Inoue JI.

Visualization of RelB expression and activation at the single-cell level during dendritic cell maturation in Relb-Venus knock-in mice.

J. Biochem., 158: 485-495 (2015)

 

Shinzawa M., Konno H., Qin J., Akiyama N., Miyauchi M, Ohashi H., Miyamoto-Sato E., Yanagawa H., Akiyama T*, and Inoue J.

Catalytic subunits of the phosphatase calcineurin interact with NF-κB-inducing kinase (NIK) and attenuate NIK-dependent gene expression.

Sci. Rep., 5: 10758 (2015)

 

Blackburn J, Kawasaki K, Porntaveetus T, Kawasaki M, Otsuka-Tanaka Y, Miake Y, Ota MS, Watanabe M, Hishinuma M, Nomoto T, Oommen S, Ghafoor S, Harada F, Nozawa-Inoue K, Maeda T, Peterková R, Lesot H, Inoue J, Akiyama T, Schmidt-Ullrich R, Liu B, Hu Y, Page A, Ramírez A, Sharpe PT and Ohazama A.

Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium.

J. Dent. Res., 94: 121-128 (2015)

 

Akiyama N., Shinzawa M., Miyauchi M., Yanai H., Tateishi R., Shimo Y., Ohshima D., Matsuo K., Sasaki I., Hoshino K., Wu G., Yagi S. Inoue J., Kaisho T., and Akiyama T*.

Limitation of immune tolerance–inducing thymic epithelial cell development by Spi-B–mediated negative feedback regulation.

J. Exp. Med., 211: 2425-2438 (2014)

 

Akiyama T*, Shiraishi T., Qin J., Konno H., Akiyama N., Shinzawa M., Miyauchi M., Takizawa N., Yanai H., Ohashi H., Miyamaoto-Sato E., Yanagawa H., Yong W., Shou W., and Inoue J.

Mitochondria–nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN

PLoS One. 9: e95992 (2014)

 

Wu G., Hirabayashi K, Sato S., Akiyama N., Akiyama T., Shiota K., and Yagi S.

DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells.

BMC Immunol. 13: 58 (2012)

 

Shinzawa M., Maruyama Y., Qin J., Akiyama N., Miyauchi M., Yanai H., Takami M., Inoue J., and *Akiyama T.

Splenic extramedullary hemopoiesis caused by a dysfunctional mutation in the NF-κB-inducing kinase gene.

Biochem. Biophys. Res. Commun., 414: 773-778 (2011)

 

Ohshima D., Qin J., Konno H., Hirosawa A., Shiraishi T., Yanai H., Shimo Y., Shinzawa M., Akiyama N., Yamashita R., Nakai K., *Akiyama T, and Inoue J.

RANK signaling induces interferon-stimulated genes in the fetal thymic stroma.

Biochem. Biophys. Res. Commun., 408: 530-536 (2011)

 

Ohno T., Oboki K., Kajiwara N., Tanaka S., Ikeda M., Iikura M., Akiyama T., Inoue J., Matsumoto K., Sudo K., Azuma M., Okumura K., Kamradt T., Saito H., Nakae S.

Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation. Plos One, 6: e18404 (2011)

 

Mouri Y., Yano M., Shinzawa M., Shimo Y., Hirota F., Nishikawa Y, Nii T., Kiyonari H., Abe T., Uehara H., Izumi K., Tamada K., Chen L., Penninger JM., Inoue J., *Akiyama T  and Matsumoto M.

Lymphotoxin Signal Promotes Thymic Organogenesis by Eliciting RANK Expression in the Embryonic Thymic Stroma.

J. Immunol., 186: 5047-5057 (2011)

 

Shimo Y., Yanai H., Ohshima D., Qin J., Motegi H., Maruyama Y., Hori S., Inoue J., and *Akiyama T.

TRAF6 directs commitment to regulatory T cells in thymocytes.

Genes Cells., 16, 437-447 (2011)

 

Motegi H., Shimo Y., Akiyama T. and Inoue J.

TRAF6 negatively regulates the Jak1-Erk pathway in interleukin-2 signaling.

Genes Cells., 16, 179-189 (2011)

 

Ishiguro A, Akiyama T, Inoue J., and Nakamura Y.

Therapeutic Potential of Anti-Interleukin-17A Aptamer: Suppression of Interleukin-17A signaling and Attenuation of autoimmunity in mouse models.

Arth. Rheu., 63, 455-466 (2011)

 

Tando T, Ishizaka A, Watanabe H, Ito T, Iida S, Haraguchi T, Mizutani T, Izumi T, Isobe T, Akiyama T, Inoue J and Iba H.

Requiem protein links RelB/p52 and the Brm-type SWI/SNF complex in a non-canonical NF-κB pathway.

J. Biol. Chem., 285: 21951-21960 (2010)

 

Ando K, Hasegawa K, Shindo K, Furusawa T, Fujino T, Kikugawa K, Nakano H, Takeuchi O, Akira S, Akiyama T, Gohda J, Inoue J, Hayakawa M.

Human lactoferrin activates NF-κB through Toll-like receptor 4 (TLR4) pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling.

FEBS J. 277, 2051-2066 (2010)

 

Ishikawa K, Akiyama T., Ito K., Semba K. and *Inoue J.

Independent stabilizations of polysomal Drg1/Dfrp1 complex and non-polysomal Drg2/Dfrp2 complex in mammalian cells.

Biochem. Biophys. Res. Commn. 390, 552-556 (2009)

 

Nagatake T, Fukuyama S, Kim D-Y, Goda K, Igarashi O, Sato S, Nochi T, Sagara H, Yokota Y, Jetten AM, Kaisho T, Akira S, Mimuro H, Sasakawa S, Fukui Y, Fujihashi K, Akiyama T, Inoue J, Penninger JM, Kunisawa J, and Kiyono H.

Id2-, RORγ-, and LTbR-independent lymphoid organogenesis in ocular immunity.

J. Exp. Med., 206, 2351-2364 (2009)

 

Konno H, Yamamoto T, Yamazaki K, Gohda J, Akiyama T, Semba K, Goto H, Kato A, Yujiri T, Imai T, Kawaguchi Y, Su B, Takeuchi O, Akira S, Tsunetsugu-Yokota Y, and Inoue J.

TRAF6 establishes innate immune responses by activating NF-kappaB and IRF7 upon sensing cytosolic viral RNA and DNA.

PLoS One., 25: e5674 (2009)

 

*Akiyama T, Shimo Y, Yanai H, Qin J, Ohsima, D, Maruyama Y, Asaumi Y, Kitazawa J, Takayanagi H, Penninger JM, Matsumoto M, Nitta T, Takahama Y, and Inoue J.

The Tumor necrosis family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance

Immunity, 29: 423-437 (2008).

 

Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yosikai Y, Inoue J, Akiyama T, and Takahama Y.

The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.

Immunity, 29, 438-450 (2008)

 

Yang Y.J., Chen W., Carrigan S.O., Chen W-M., Roth K., Akiyama T., Inoue J., Marshall J.S., Berman J.N. and Lin Y-J.

TRAF6 specifically contributes to FceRI-mediated cytokine production but not mast cell degranulation.

J. Biol. Chem., 283, 32110-32118 (2008).

 

Qin J, Konno H, Ohshima D, Yanai H, Motegi H, Shimo Y, Hirota F, Matsumoto M, Takaki S, Inoue J, and *Akiyama T.

Developmental stage-dependent collaboration between the TRAF6 and lymphotoxin pathways for B-cell follicle organization in secondary lymphoid organs.

J. Immunol. 179, 6799-6807 (2007)

 

Ito H, Esashi E, Akiyama T, Inoue J, and Miyajima A.

IL-18 produced by thymic epithelial cells induces development of dendritic cells with CD11b in the fetal thymus.

Int. Immunol., 18: 1253-1263 (2006)

 

Akiyama T, Maeda S, Yamane S, Ogino K, Kasai M, Kajiura F, Matsumoto M, and Inoue J.

Dependence of Self-tolerance on TRAF6-directed Development of Thymic Stroma. Science, 308: 248-251 (2005)