論文 - 高橋　勇人

尋常性天疱瘡

高橋勇人

Visual Dermatology 14 （ 9 ） 1070 - 1074 2015年08月

Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: Survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR)

Kano, Y. Tohyama, M. Aihara, M. Matsukura, S. Watanabe, H. Sueki, H. Iijima, M. Morita, E. Niihara, H. Asada, H. Kabashima, K. Azukizawa, H. Hashizume, H. Nagao, K. Takahashi, H. Abe, R. Sotozono, C. Kurosawa, M. Aoyama, Y. Chu, C. Y. Chung, W. H. Shiohara, T.

Journal of Dermatology 42 （ 3 ） 276 - 282 2015年03月

査読有り

皮膚疾患におけるT細胞の重要な役割

高橋 勇人 天谷雅行

実験医学 32 （ 17 ） 2854 - 2860 2014年11月

共著

デスモグレイン3に対する液性および細胞性の自己免疫応答

高橋 勇人

アレルギー・免疫 21 （ 11 ） 1693 - 1700 2014年10月

単著

薬疹の重症化をもたらす要因

高橋 勇人

アレルギー・免疫 21 （ 8 ） 1208 - 1213 2014年08月

単著

アバタセプトによる乾癬様皮疹を呈した１例

伊東可寛 渡邊絵美子 高橋 勇人 谷川瑛子 亀田秀人 天谷雅行

臨床皮膚科 68 （ 6 ） 398 - 402 2014年05月

共著

　概要を見る

論文

Type I IFN induces binding of STAT1 to BCL6: Divergent roles of stat family transcription factors in the T follicular helper cell genetic program

Nakayamada, S. Poholek, A. C. Lu, K. T. Takahashi, H. Kato, M. Iwata, S. Hirahara, K. Cannons, J. L. Schwartzberg, P. L. Vahedi, G. Sun, H. W. Kanno, Y. O'Shea, J. J.

Journal of Immunology 192 （ 5 ） 2156 - 2166 2014年03月

査読有り

Immune response involving the bulge region in addition to telogen conversion contributes to hair loss in a case of atypical drug-induced hypersensitivity syndrome

Watanabe-Okada, E. Nagao, K. Takahashi, H. Amagai, M. Ohyama, M.

J Dermatol 40 （ 11 ） 928 - 929 2013年11月

研究論文（学術雑誌）, 共著, 査読有り

Th17 cells carrying TCR recognizing epidermal autoantigen induce psoriasis-like skin inflammation

Nishimoto, S. Kotani, H. Tsuruta, S. Shimizu, N. Ito, M. Shichita, T. Morita, R. Takahashi, H. Amagai, M. Yoshimura, A.

Journal of Immunology 191 （ 6 ） 3065 - 3072 2013年09月

Ectopic expression of epidermal antigens renders the lung a target organ in paraneoplastic pemphigus

Hata, T. Nishimoto, S. Nagao, K. Takahashi, H. Yoshida, K. Ohyama, M. Yamada, T. Asano, K. Amagai, M.

Journal of Immunology 191 （ 1 ） 83 - 90 2013年07月

BACH2 represses effector programs to stabilize T reg-mediated immune homeostasis

Roychoudhuri R., Hirahara K., Mousavi K., Clever D., Klebanoff C.A., Bonelli M., Sciumè G., Zare H., Vahedi G., Dema B., Yu Z., Liu H., Takahashi H., Rao M., Muranski P., Crompton J.G., Punkosdy G., Bedognetti D., Wang E., Hoffmann V., Rivera J., Marincola F.M., Nakamura A., Sartorelli V., Kanno Y., Gattinoni L., Muto A., Igarashi K., O'Shea J.J., Restifo N.P.

Nature （Nature）  498 （ 7455 ） 506 - 510 2013年06月

査読有り,  ISSN  00280836

　概要を見る

Through their functional diversification, distinct lineages of CD4 + T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma, Crohn's disease, coeliac disease, vitiligo, multiple sclerosis and type 1 diabetes. Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4+ T cells. BACH2 was required for efficient formation of regulatory (T reg) cells and consequently for suppression of lethal inflammation in a manner that was Treg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within TH 1, TH 2 and TH 17 cell lineages. These findings identify BACH2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity. © 2013 Macmillan Publishers Limited. All rights reserved.

• Access to Document (DOI)

BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis

Roychoudhuri, R. Hirahara, K. Mousavi, K. Clever, D. Klebanoff, C. A. Bonelli, M. Sciume, G. Zare, H. Vahedi, G. Dema, B. Yu, Z. Liu, H. Takahashi, H. Rao, M. Muranski, P. Crompton, J. G. Punkosdy, G. Bedognetti, D. Wang, E. Hoffmann, V. Rivera, J. Marincola, F. M. Nakamura, A. Sartorelli, V. Kanno, Y. Gattinoni, L. Muto, A. Igarashi, K. O'Shea, J. J. Restifo, N. P.

Nature 498 （ 7455 ） 506 - 510 2013年06月

研究論文（学術雑誌）, 共著, 査読有り

Distinct requirements for T-bet in gut innate lymphoid cells

Sciume, G. Hirahara, K. Takahashi, H. Laurence, A. Villarino, A. V. Singleton, K. L. Spencer, S. P. Wilhelm, C. Poholek, A. C. Vahedi, G. Kanno, Y. Belkaid, Y. O'Shea, J. J.

J Exp Med 209 （ 13 ） 2331 - 2338 2012年12月

研究論文（学術雑誌）, 共著, 査読有り

STATs shape the active enhancer landscape of T cell populations

Vahedi, G. Takahashi, H. Nakayamada, S. Sun, H. W. Sartorelli, V. Kanno, Y. O'Shea, J. J.

Cell 151 （ 5 ） 981 - 993 2012年11月

査読有り

TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

Takahashi H., Kanno T., Nakayamada S., Hirahara K., Sciumè G., Muljo S.A., Kuchen S., Casellas R., Wei L., Kanno Y., O'Shea J.J.

Nature Immunology （Nature Immunology）  13 （ 6 ） 587 - 595 2012年06月

査読有り,  ISSN  15292908

　概要を見る

Distinct CD4+ T cell subsets are critical for host defense and immunoregulation. Although these subsets can act as terminally differentiated lineages, they have been increasingly noted to demonstrated plasticity. MicroRNAs are factors that control T cell stability and plasticity. Here we report that naturally occurring regulatory T cells (Treg cells) had high expression of the microRNA miR-10a and that miR-10a was induced by retinoic acid and transforming growth factor-β (TGF-β) in inducible T reg cells. By simultaneously targeting the transcriptional repressor Bcl-6 and the corepressor Ncor2, miR-10a attenuated the phenotypic conversion of inducible Treg cells into follicular helper T cells. We also found that miR-10a limited differentiation into the TH17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells. © 2012 Nature America, Inc. All rights reserved.

• Access to Document (DOI)

Helper T cell diversity and plasticity

Nakayamada, S. Takahashi, H. Kanno, Y. O'Shea, J. J.

Curr Opin Immunol 24 （ 3 ） 297 - 302 2012年06月

共著

TGF-beta and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

Takahashi, H. Kanno, T. Nakayamada, S. Hirahara, K. Sciume, G. Muljo, S. A. Kuchen, S. Casellas, R. Wei, L. Kanno, Y. O'Shea, J. J.

Nature Immunology 13 （ 6 ） 587 - 595 2012年06月

研究論文（学術雑誌）, 共著, 査読有り

Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1

Hirahara, K. Ghoreschi, K. Yang, X. P. Takahashi, H. Laurence, A. Vahedi, G. Sciume, G. Hall, A. O. Dupont, C. D. Francisco, L. M. Chen, Q. Tanaka, M. Kanno, Y. Sun, H. W. Sharpe, A. H. Hunter, C. A. O'Shea, J. J.

Immunity 36 （ 6 ） 1017 - 1030 2012年06月

研究論文（学術雑誌）, 共著, 査読有り

Early Th1 Cell Differentiation Is Marked by a Tfh Cell-like Transition

Nakayamada, S., Kanno, Y., Takahashi, H., Jankovic, D., Lu, K., Johnson, T., Sun, H.-W., Vahedi, G., Hakim, O., Handon, R., Schwartzberg, P.L., Hager, G., O'Shea, J.

Immunity 35 （ 6 ） 919 - 931 2011年12月

Desmoglein 3-specific CD4⁺ T cells induce pemphigus vulgaris and interface dermatitis in mice

Takahashi H., Kouno M., Nagao K., Wada N., Hata T., Nishimoto S., Iwakura Y., Yoshimura A., Yamada T., Kuwana M., Fujii H., Koyasu S., Amagai M.

Journal of Clinical Investigation （Journal of Clinical Investigation）  121 （ 9 ） 3677 - 3688 2011年09月

査読有り,  ISSN  00219738

　概要を見る

Pemphigus vulgaris (PV) is a severe autoimmune disease involving blistering of the skin and mucous membranes. It is caused by autoantibodies against desmoglein 3 (Dsg3), an adhesion molecule critical for maintaining epithelial integrity in the skin, oral mucosa, and esophagus. Knowing the antigen targeted by the autoantibodies renders PV a valuable model of autoimmunity. Recently, a role for Dsg3-specific CD4+ T helper cells in autoantibody production was demonstrated in a mouse model of PV, but whether these cells exert cytotoxicity in the tissues is unclear. Here, we analyzed 3 Dsg3-specific TCRs using transgenic mice and retrovirus induction. Dsg3-specific transgenic (Dsg3H1) T cells underwent deletion in the presence of Dsg3 in vivo. Dsg3H1 T cells that developed in the absence of Dsg3 elicited a severe pemphigus-like phenotype when cotransferred into immunodeficient mice with B cells from Dsg3-/- mice. Strikingly, in addition to humoral responses, T cell infiltration of Dsg3-expressing tissues led to interface dermatitis, a distinct form of T cell-mediated autoimmunity that causes keratinocyte apoptosis and is seen in various inflammatory/autoimmune skin diseases, including paraneoplastic pemphigus. The use of retrovirally generated Dsg3-specific T cells revealed that interface dermatitis occurred in an IFN-γ- and TCR avidity-dependent manner. This model of autoimmunity demonstrates that T cells specific for a physiological skin-associated autoantigen are capable of inducing interface dermatitis and should provide a valuable tool for further exploring the immunopathophysiology of T cell-mediated skin diseases.

• Access to Document (DOI)