Experimental Immunology

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One of the key mechanisms of immunological self-tolerance (i.e., unresponsiveness to self-constituents) is T cell-mediated dominant control of self-reactive lymphocytes. We have shown that CD25+CD4+ regulatory T (Treg) cells, which are naturally produced in the immune system, are actively engaged in suppressive control of a variety of physiological and pathological immune responses including autoimmune responses. Dysfunction or deficiency of CD25+CD4+ natural Treg cells is indeed a cause of autoimmune disease, allergy, and inflammatory bowel disease in humans. On the other hand, reduction of Treg cells or attenuation of their suppressive activity is able to enhance immune responses such as those against tumor antigens or microbes, while the increase in number or potentiation of their suppressive activity can establish immunological tolerance to organ grafts. A key feature of natural Treg cells is that they express the transcription factor Foxp3 as a master control gene for their development and function. One of the research projects of this laboratory is to determine the molecular and cellular basis of Treg development and function, in particular, how Foxp3 controls other genes and confer suppressive activity to Treg cells, how they are produced in the normal immune system, and how they can be exploited to control immune responses in clinical settings such as autoimmune disease.

Another project is to decipher how autoimmune disease, in particular rheumatoid arthritis, develops as a result of genetic anomaly of the immune system. We have established a mouse model in which T cell-mediated autoimmune arthritis spontaneously develops because of a point mutation of the gene encoding ZAP70, a key signaling molecule in T cells. The anomaly changes the thresholds of T cells to thymic selection, leading to positive selection of otherwise negatively selected autoimmune T cells. This "selection shift" of the T-cell repertoire towards high self-reactivity results in thymic production of pathogenic autoimmune T cells including arthritogenic T cells. We hope that genetic and molecular analysis of this model of autoimmune disease will facilitate our understanding of how genetic, environmental, and immunological factors altogether contribute to the development of T cell-mediated autoimmune disease in humans.

Principal Investigator

Shimon Sakaguchi Professor

Research field:Immunology (Immunological tolerance and autoimmune disease)
+81-6-6879-4461
shimon atmarkifrec.osaka-u.ac.jp
Education history
1970-1972Kyoto University Premedical Course
1972-1976 Kyoto University Medical School
Research and career history
1999- Professor and Chair, Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University
2007- Director, Institute for Frontier Medical Sciences, Kyoto University

Members

Naganari Ohkura Professor
nohkura atmark ifrec.osaka-u.ac.jp
Keiji Hirota Guest Associate Professor
hkeiji atmark ifrec.osaka-u.ac.jp
Noriko Sakaguchi Visiting Academic Staff
norikos atmark ifrec.osaka-u.ac.jp
Wing James Badger Assistant Professor
jbwing atmark ifrec.osaka-u.ac.jp
Norihisa Mikami Visiting Academic Staff
mikami atmark ifrec.osaka-u.ac.jp
Atsushi Tanaka Assistant Professor
atanaka atmark ifrec.osaka-u.ac.jp
Kenji Ichiyama Assistant Professor
ichiken atmark ifrec.osaka-u.ac.jp
Jun Huang Researcher
HuangJun2023 atmark ifrec.osaka-u.ac.jp
Hu Daniel Yuning Researcher
daniel-hu atmark ifrec.osaka-u.ac.jp
Tay Christopher Jian Wei Researcher
ctayjw atmark ifrec.osaka-u.ac.jp
Ee Lyn Lim Researcher
eelynlim atmark ifrec.osaka-u.ac.jp
 
 

Publications

Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science. 346:1536-1540, 2014.
Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S. Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease. Science. 346:363-368, 2014.
Wing JB, Ise W, Kurosaki T, Sakaguchi S. Regulatory T-cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. Immunity. 41:1013-1025,2014.
Yamazaki S, Nishioka A, Kasuya S, Ohkura N, Hemmi H, Kaisho T, Taguchi O, Sakaguchi S, Morita A. Homeostasis of Thymus-Derived Foxp3+ Regulatory T Cells Is Controlled by Ultraviolet B Exposure in the Skin. J Immunol. 193:5488-5497, 2014 .
Kitagawa Y, Ohkura N, Sakaguchi S. Epigenetic control of thymic Treg-cell development. Eur. J. Immunol. 2014 Oct 28.
Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nago-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest A, Standley D, Date D, Sakaguchi S, and the FANTOM consortium. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. PNAS. 111: 5289-5294, 2014.
Mikami N, Sakaguchi S. CD28 signals the differential control of regulatory T cells and effector T cells. Eur J Immunol. 44:955-957, 2014.
Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nat Rev Rheumatol. 10:543-551 2014.
Morikawa H, Sakaguchi S. Genetic and epigenetic basis of Treg cell development and function: From a FoxP3-centered view to an epigenome-defined view of natural Treg cells. Immunol. Rev. 259: 192-205, 2014.
Forrest A, ..., Morikawa H., ..., Hamaguchi M., ..., Ohkura N., ...,Sakaguchi S., ...,Hayashizaki Y, et al., A promoter level mammalian expression atlas. Nature. 507: 462-470, 2014.
Wing JB, Sakaguchi S. Foxp3+ Treg cells in humoral immunity. Int Immunol. 26: 61-69, 2014.
Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 27: 1-7, 2014.
Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jager E, and Sakaguchi S. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking anti-tumor immune responses in humans. PNAS. 110:17945-17950, 2013.
Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 500:232-236, 2013.
Ohkura N, Kitagawa Y, Sakaguchi S. Development and Maintenance of Regulatory T cells. Immunity. 38:414-423, 2013.
Yamaguchi T, Kishi A, Osaki M, Morikawa H, Prieto-Martin P, Wing K, Saito T, and Sakaguchi S. Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. PNAS, 110(23):E2116-2125, 2013.
Sakaguchi S, Vignali DAA, Niec, RE, Rudensky AY, and Waldmann H. Regulatory T cell plasticity and stability. Nat. Rev. Immunol. 13:461-467, 2013.
Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 14:307-308, 2013.
Ohkura N, Sakaguchi S. Treg cells acquire new directions, cytokines navigate. Immunity. 37:443-4, 2012.
Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, Osaki M, Tanaka Y, Yamashita R, Nakano N, Huehn J, Fehling HJ, Sparwasser T, Nakai K, Sakaguchi S. T cell receptor stimulation-induced epigenetic changes and foxp3 expression are independent and complementary events required for Treg cell development. Immunity. 37:785-99, 2012.
Noguchi, T., Kato, T., Wang, L., Maeda, Y., Ikeda, H., Sato, E., Knuth, A., Gnjatic, S., Ritter, G., Sakaguchi, S., Old, L. J., Shiku, H., and Nishikawa, H. Intracellular tumor-associated antigens represent effective targets for passive immunotherapy. Cancer Res. 72:1672-1682, 2012.
Hamaguchi M, Sakaguchi S. Regulatory T cells expressing PPAR-γ control inflammation in obesity. Cell Metab. 16:4-6, 2012.
Wing JB, Sakaguchi S. Multiple treg suppressive modules and their adaptability. Front Immunol. 3:178. Epub 2012.
Nishikawa, H., Maeda, Y., Ishida, T., Gnjatic, S., Sato, E., Mori, F., Sugiyama, D., Ito, A., Fukumori, Y., Utsunomiya, A., Inagaki, H., Old, L. J., Ueda, R., and Sakaguchi, S. Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. Blood. 119:3097-3104, 2012.
Sakaguchi, S., Benham, H., Cope, A. P., Thomas, R. T-cell receptor signaling and the pathogenesis of autoimmune arthritis: insights from mouse and man. Immunol Cell Biol. 90:277-87, 2012.
Sakaguchi, S., Powrie, F., Ransohoff, R. M. Re-establishing immunological self-tolerance in autoimmune disease. Nat Med. 18:54-58, 2012.
Ohe, H., Waki, K., Yoshitomi, M., Morimoto, T., Nafady-Hego, H., Satoda, N., Li, Y., Zhao, X., Sakaguchi, S., Uemoto, S., Bishop, G. A., Koshiba, T. Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match. Transpl Int. 25:97-106, 2012.
Yoshioka, Y., Ono, M., Osaki, M., Konishi, I., Sakaguchi, S. Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation. Eur J Immunol. 42:749-759, 2012.
Wing, K., Yamaguchi, T., Sakaguchi, S. Cell-autonomous and ?nonautonomous functions of CTLA-4 for negative control of immune responses. Trends Immunol. 32:428-433, 2011.
Sakaguchi, S., Wing K. Damping by depletion. Science. 332:542-543, 2011.
Ohkura, N., Sakaguchi, S. Maturation of effector regulatory T cells. Nat Immunol. 12:283-284, 2011.
Yamaguchi, T., Wing, J. B., Sakaguchi, S. Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 23:424-430, 2011.
Sakaguchi, S., Tanaka, S., Tanaka, A., Ito, Y., Maeda, S., Sakaguchi, N., Hashimoto, M. Thymus, innate immunity and autoimmune arthritis: interplay of gene and environment. FEBS Lett. 585:3633-3639, 2011.
Wing, J. B., Sakaguchi, S. TCR diversity and Treg cells, sometimes more is more. Eur J Immunol. 41:3097-3100, 2011.
Ohkura, N., Hamaguchi, M., Sakaguchi, S. FOXP3(+) regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends Pharmacol. Sci. 32:158-66, 2011.
Ohe, H., Li, Y., Nafady-Hego, H., Kayo, W., Sakaguchi, S., Wood, K., Calne, R., Uemoto, S., Koshiba, T. Minimal but essential doses of immunosuppression: A more realistic approach to improve long-term outcomes for pediatric living-donor liver transplantation. Transplantation. 91:808-810, 2011.
Satou, Y., Yasunaga, J., Zhao, T., Yoshida, M., Miyazato, P., Takai, K., Shimizu, K., Ohshima, K., Green, P. L., Ohkura, N., Yamaguchi, T., Ono, M., Sakaguchi, S., Matsuoka, M. HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLoS Pathog. 7(2):e1001274, 2011.
Miyara, M., Gorochov, G., Ehrenstein, M., Musset, L., Sakaguchi, S., Amoura, Z. Human FoxP3(+) regulatory T cells in systemic autoimmune diseases. Autoimmun. Rev. 10:744-755, 2011.
Miyara, M., and Sakaguchi, S. FoxP3+CD4+ regulatory T cells: their knowns and unknowns. Immunol. Cell. Biology. 89:346-351, 2011.
Sakaguchi, S. Regulatory T cells: history and perspective. Methods in Molecular Biology. 77: 1-13, 2011.
Ohkura N, Sakaguchi S. Foxo1 and Foxo3 help Foxp3. Immunity. 33:835-7, 2010.
Fujii, H., Arakawa, A., Kitoh, A., Miyara, M., Kato, M., Kore-Eda, S., Sakaguchi, S., Miyachi, Y., Tanioka, M., and Ono, M. Perturbations of both non-regulatory and regulatory FOXP3(+) T cells in patients with malignant melanoma. Br. J. Dermatol. 164:1052-1060, 2010.
Sakaguchi, S. Conditional stability of T cells. Nature. 468:41-42, 2010.
Nafady-Hego, H., Li, Y., Ohe, H., Zhao, X., Satoda, N., Sakaguchi, S., Wood, K., Uemoto, S., and Koshiba, T. The generation of donor-specific CD4+CD25++CD45RA+ naive regulatory T cells in operationally tolerance patients after pediatric living-donor liver transplantation. Transplantation. 90:1547-55, 2010.
Mitsui, J., Nishikawa, H., Muraoka, D., Wang, L., Noguchi, T., Sato, E., Kondo, S., Allison, J. P., Sakaguchi, S., Old, L. J., Kato, T., and Shiku, H. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin. Cancer Res. 16:2781-91, 2010.
Nishikawa, H., and Sakaguchi, S. Regulatory T cells in tumor immunity. Int. J. Cancer. 127:759-67, 2010.
Ohkura, N., and Sakaguchi, S. Regulatory T cells: roles of Tcell erceptor for their development and function. Semin. Immunopathol. 32:95-106, 2010.
Sakaguchi, S., Miyara, M., Costantino, C. M., and Hafler, D. A. FOXP3+ regulatory T cells in the human system. Nat. Rev. Immunol. 185:2295-305, 2010.
Hashimoto, M., Hirota, K., Yoshitomi, H., Maeda, S., Teradaira, S., Akizuki, S., Prieto-Martin, P., Nomura, T., Sakaguchi, N., Kohl, J., Heyman, B., Takahashi, M., Fujita, T., Mimori, T., Sakaguchi, S. Complement drives Th-17 cell differentiation and triggers autoimmune disease. J. Exp. Med. 207:1135-43, 2010.
Tanaka, S., Maeda, S., Hashimoto. M., Teradaira, S., Hirota,K., Yoshitomi, H., Katakai, T., Shimizu, A., Nomura, T., Sakaguchi, N., and Sakaguchi, S. Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J. Immunol. 185:2295-305, 2010.
Wing, K., and Sakaguchi, S. Regulatory T cells exert checks and balances on self-tolerance and autoimmunity. Nat. Immunol. 11:7-13, 2010.
Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int. Immunol. 21:1105-11, 2009.
Kitoh, A., Ono, M., Naoe, Y., Ohkura, N., Yamaguchi, T, Yaguchi, H., Kitabayashi, I., Tsukada, T., Nomura, T., Miyachi,Y., Taniuchi, I., and Sakaguchi, S. Indispensable role of Runx1/Cbfb complexes for in vivo suppressive function of FoxP3+ regulatory T cells. Immunity. 31:609-620, 2009.
Sakaguchi, S., Wing, K., and Yamaguchi, T. Dynamics of peripheral tolerance and immune regulation. Eur. J. Immunol. 39(9):2331-6, 2009.
Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Mimori T. Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. Arthritis Rheum. 60:2294-2303, 2009.
Miyara, M., Wing, K., and Sakaguchi, S. Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansion. J Allergy Clin Immunol. 123:749-55, 2009.
Ohkura, N,. and Sakaguchi, S. A novel modifier of regulatory T cells Nat Immunol. 10: 685-686, 2009.
Miyara, M., Shima, T., Kitoh, A., Yoshioka, Y., Niwa, A., Taflin, C., Heike, T., Valeyre, D., Mathian, A., Nakahata, T., Yamaguchi T., Nomura, T., Wing, K., Ono, M., Amoura, Z., Guy Gorochov, G., and Sakaguchi, S. Functional delineation and differentiation dynamics of human CD4(+) T cells expressing the FoxP3 transcription factor. Immunity. 30:899-911, 2009.
Nagahama, K., Fehervari, Z., Oida, T., Ogawa, O., and Sakaguchi, S. Differential control of alloantigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation tolerance. Int.Immunol. 21:379-391, 2009.
Yoshitomi, M., Koshiba, T., Haga, H., Li, Y., Zhao, X., Cheng, D., Miyagawa, A., Sakashita, H., Tsuruyama T., Ueda, M., Wood, K., Sakaguchi S., Manabe, T., Tanaka, K., and Uemoto, S. Requirement of protocol biopsy before and after complete cessation of immunosuppression following liver transplantation. Transplantation. 87:606-614, 2009.
Wing K, and Sakaguchi S. Regulatory T cells. In Clinical Immunology, eds. R. R. Rich, T. A. Fleisher, W. T. Shearer, H. W. Schroeder, Jr., A. J. Frew, and C. M. Weyand, Mosby. 2008; P249-258.
Miyara, M., and Sakaguchi, S. Regulatory T Cells and the Control of Auto-Immunity: From day 3 Thymectomy to FoxP3+ Regulatory T Cells. In Regulatory T cells and Clinical Application, Ed. S. Jiang, Springer, p3-16, 2008.
Sakihama T, Sato T, Iwanari H, Kitamura T, Sakaguchi S, Kodama T, Hamakubo T. A simple detection method for low-affinity membrane protein interactions by baculoviral display. PLoS ONE. 2008;3(12):e4024.
Satoda N, Shoji T, Wu Y, Fujinaga T, Chen F, Aoyama A, Zhang JT, Takahashi A, Okamoto T, Matsumoto I, Sakai H, Li Y, Zhao X, Manabe T, Kobayashi E, Sakaguchi S, Wada H, Ohe H, Uemoto S, Tottori J, Bando T, Date H, Koshiba T. Value of FOXP3 Expression in Peripheral Blood as Rejection Marker After Miniature Swine Lung Transplantation. J. Heart Lung Transplant. 27:1293-1301, 2008.
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., and Sakaguchi, S. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 322:271-275, 2008.
Li, Y., Zhao, X., Cheng, D., Haga, H., Tsuruyama, T., Wood, K., Sakaguchi, S., Tanaka, K., Uemoto, S., and Koshiba, T. The presence of FOXP3 expressing T cells within grafts of tolerance human liver transplant recipients. Transplantation. 86:1837-1843,2008
Wakasa-Morimoto, C., Toyosaki-Maeda, T., Matsutani, T., Yoshida, R., Nakamura-Kikuoka, S., Maeda-Tanimura, M., Yoshitomi, H., Hirota, K., Hashimoto, H., Masaki, H., Fujii, F., Sakata, T., Tsuruta, Y., Suzuki, R., Sakaguchi, N., and Sakaguchi, S. Arthritis and pneumonitis produced by the same T-cell clones from mice with spontaneous autoimmune arthritis. Int. Immunol. 20:1331-1342, 2008.
Onishi, Y., Fehervari, Z., Yamaguchi, T., and Sakaguchi, S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl. Acad. Sci. USA. 29:10113-10118, 2008.
Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. Regulatory T cells and immune tolerance. Cell. 133: 775-787, 2008.
Sakaguchi, S. Regulatory T cells in the past and for the future. Eur. J. Immunol. 38:901-937, 2008.
Yamaguchi T, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. 27:145-159, 2007.
Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S. Foxp3 controls regulatory T cell function via interacting with AML1/Runx1. Nature. 446:685-689, 2007.
Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, Yamaguchi T, Nomura T, Ito H, Nakamura T, Sakaguchi N, Sakaguchi S. Preferential recruitment of arthritogenic Th17 cells to inflamed joints via CCR6/CCL20 in rheumatoid arthritis and its animal model. J. Exp. Med. 204:2803-2812, 2007
Sakaguchi S, Powrie F. Emerging challenges in regulatory T cell function and biology. Science. 317:627-629, 2007.
Sakaguchi S, Wing K, Miyara M. Regulatory T cells in brief history and perspective. Eur. J. Immunol. 37:s116-123, 2007
Nomura T, Sakaguchi S. Foxp3 and Aire in thymus-generated T(reg) cells: a link in self-tolerance. Nat Immunol. 8:333-334, 2007.
Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 13:108-116, 2007.
Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med. 204:41-47, 2007.
Yamaguchi T, Sakaguchi S. Skin controls immune regulators. Nat Med. 12:1358-1359, 2006.
Katakai T, Nomura T, Gonda H, Sugai M, Agata Y, Nishio A, Masuda T, Sakaguchi S, Shimizu A. Spontaneous Large-Scale Lymphoid Neogenesis and Balanced Autoimmunity versus Tolerance in the Stomach of H+/K+-ATPase-Reactive TCR Transgenic Mouse. J Immunol. 177:7858-67, 2006.
Wing, K. and Sakaguchi, S. Regulatory T cells in allergy. Curr. Opin. Allergy and Immunol. 6:482-8, 2006.
Fehervari, Z. and Sakaguchi, S. Peacekeepers of the immune system. Sci Am. 295:56-63, 2006.
Wing, K., Fehervari, Z., and Sakaguchi, S. Emerging possibilities in the development and function of regulatory T cells. Int. Immunol. 18:991-1000, 2006.
Sugimoto, N., Oida, T., Hirota, K., Nakamura, K., Nomura, T., Uchiyama, T., and Sakaguchi, S. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 18:1197-1209, 2006.
Nishioka, T., Shimizu, J, Iida, R., Yamazaki, S., and Sakaguchi, S. CD4+ CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice. J. Immunol. 176:6586-6593, 2006.
Sakaguchi, S., Ono, M., Setoguchi, R., Hori, S., Fehervari, Z., Shimizu, J., Takahashi, T., and Nomura, T. Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol. Rev. 212:8-27, 2006.
Ono, M., Shimizu, J., Miyachi, Y., and Sakaguchi, S. Induction of fatal autoimmune myocarditis and other autoimmune diseases in mice by depleting Foxp3-expressing naturally arising CD4+ regulatory T cells. J. Immunol. 176:4748-4756, 2006.
Fehervari, Z., Yamaguchi, T., and Sakaguchi, S. The dichotomous roles of IL-2: tolerance versus immunity. Trends Immunol. 27:109-111, 2006.
Sakaguchi, S., Sakaguchi, N., Yoshitomi, H., Hata, H., Takahashi, T., and Nomura, T. Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1. Semin. Immunol. 18:199-206, 2006.
Yamaguchi, T. and Sakaguchi, S. Regulatory T cells in immune surveillance and treatment of cancer. Semin. Cancer Biol. 16:115-123, 2006.
Sakaguchi, S., Takahashi, T., Hata, H., Yoshitomi, H., Tanaka, S., Hirota, K., Nomura, T., and Sakaguchi, N. SKG mice, a monogenic model of autoimmune arthritis due to altered signal transduction in T cells. In The hereditary Basis of Rheumatic Diseases, Progress in Inflammation Research. Edited by RikardHolmdahl, Birkhaeuser Verlag, Basel, p147-159, 2006.
Sakaguchi, S., Setoguchi, R., Yagi, H., and Nomura, T. Naturallyarising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease. Curr Top Microbiol Immunol. 305:51-66, 2006.
Fehervari, Z. and Sakaguchi, S. T lymphocytes: Regulatory. Nature Encyclopedia of Life Sciences. Wiley Interscience, 2006. Available at www.els.net.
Sakaguchi, S., Sakaguchi, N. Animal models of arthritis caused by systemic alteration of the immune system. Curr Opin Immunol. 17: 589-594, 2005.
Ko, K., Yamazaki, S., Nakamura, K., Nishioka, T., Hirota, K., Yamaguchi, T., Shimizu, J., Nomura, T., Chiba, T., and Sakaguchi, S. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J. Exp. Med. 202: 885-891, 2005.
Nishikawa, H., Kato, T., Tawara, I., Saito, K., Ikeda, H., Kuribayashi, K., Allen, P. M., Schreiber, R. D., Sakaguchi, S., Old, L. J., Shiku, H. Definition of target antigens for naturally occurring CD4+CD25+ regulatory T cells. J. Exp. Med. 201: 681-686, 2005.
Sakaguchi, S., and Sakaguchi, N. History of CD25+CD4+ regulatory T cells. In Regulatory T cells in inflammation, Progress in Inflammation Research. Eds. L. S. Taams, A. N. Akbar, and M. H. M. Wauben, Birkhaeuser Verlag, Basel, p3-17, 2005.
Nomura, T., and Sakaguchi, S. Regulatory T cells in tumor immunity. Curr Top Microbiol Immunol. 293:287-302, 2005.
Sakaguchi, S. and Sakaguchi, N. Regulatory T cells in immunologic self-tolerance and autoimmune diseases. Int. Rev. Immunol. 24:211-226, 2005.
Fehervari Z, Sakaguchi S. CD4+ regulatory cells as a potential Immunotherapy. Philos Trans R Soc Lond B Biol Sci. 360:1647-1661, 2005.
Sakaguchi, S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6: 345-352, 2005.
Kuroda N, Mitani T, Takeda N, Ishimaru N, Arakaki R, Hayashi Y, Bando Y, Izumi K, Takahashi T, Nomura T, Sakaguchi S, Ueno T, Takahama Y, Uchida D, Sun S, Kajiura F, Mouri Y, Han H, Matsushima A, Yamada G, Matsumoto M. Development of Autoimmunity against Transcriptionally Unrepressed Target Antigen in the Thymus of Aire-Deficient Mice. J. Immunol. 174:1862-1870, 2005.
Setoguchi, R., Hori, S., Takahashi, T., and Sakaguchi, S. Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization J. Exp. Med. 201:723-735, 2005.
Yoshitomi, H., Sakaguchi, N., Brown, G., Tagami, T., Sakihama,T., Nomura, T., Akira, S., Gordon, S., Nakamura, T., and Sakaguchi, S. Environmental stimulation of innate immunity triggers chronic arthritis in mice genetically prone to produce arthritogenic autoimmune T cells: a key role of fungal β-glucans and their receptor Dectin-1. J. Exp. Med. 201: 949-960, 2005.
Fehervari, Z., and Sakaguchi, S.: Regulatory T cells. In Measuring Immunity, eds. M. T. Lotze and A. W. Thompson, Elsevier. p322-335, 2005. Fehervari, Z., and Sakaguchi, S. CD4+ regulatory T cells and immune control. J. Clin. Invest. 114:1209-117, 2004.
Yagi, H., Nomura, T., Nakamura, K., Kitawaki, T., Hori, S., Maeda, M., Onodera, M., Uchiyama, T., Fujii, S., and Sakaguchi, S. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol. 16: 1643-1656, 2004.
Kanamaru, F., Youngnak, P., Hashiguchi, M., Nishioka, T., Takahashi, T., Sakaguchi, S., Ishikawa, I., and Azuma, M. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J. Immunol. 172: 7306-7314, 2004.
Fehervari, Z., and Sakaguchi, S.: Control of CD25+CD4+ regulatory T cell activation and function by dendritic cells. Int. Immunol. 16:1769-1780, 2004.
Hata, H., Sakaguchi, N., Yoshitomi, H., Iwakura, Y., Sekikawa, K., Rennick, D., Azuma, Y., Kanai, C., Moriizumi, E., Nakamura, T., and Sakaguchi, S. Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J. Clin. Invest. 114: 582-588, 2004.
Nishimura, E., Sakihama, T., Setoguchi, R., Tanaka. K., and Sakaguchi, S. Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising CD25+CD4+ regulatory T cells. Int. Immunol. 16: 1189-1201, 2004.
Dittmer, U., He, H., Messer, R. J., Schimmer, S., Olbrich, A. R., Ohlen, C., Greenberg, P. D., Stromnes, I. M., Iwashiro, M., Sakaguchi, S., Evans, L. H., Peterson, K. E., Yang, G., Hasenkrug, K. J. Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity. 20: 1-20, 2004.
Fehervari, Z., and Sakaguchi, S. Development and function of CD25+CD4+ regulatory T cells. Curr Opin Immunol. 16:203-208, 2004.
Hori, S., and Sakaguchi, S. Foxp3, a critical regulator of regulatory T cell development and function. Microbes Infect. 6: 745-51, 2004.
Sakaguchi, S.: Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22:531-562, 2004.
Kajiura, F., S. Sun, T. Nomura, K. Izumi, T. Ueno, Y. Bando, N. Kuroda, H. Han, Yi Li, A. Matsushima, Y. Takahama, S. Sakaguchi, T. Mitani and M. Matsumoto. NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner. J. Immunol. 172: 2067-2075, 2004.
Sakaguchi, S. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 112: 1310-1312, 2003.
Sakaguchi, N., Takahashi, T., Hata, H., Nomura, T., Tagami, T., Yamazaki, S., Sakihama, T., Matsutani, T., Negishi, I., Nakatsuru, S., and Sakaguchi, S. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 426:454-60, 2003
Sakaguchi, S. Taming transplantation by regulatory T cells. Nat Med. 9:1117-1118, 2003.
Takahashi, T. and Sakaguchi, S. Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease. Curr. Mol. Med. 3: 693-706, 2003.
Hori, S., Takahashi, T., and Sakaguchi, S. Control of autoimunity by natural regulatory T cells. Adv. Immunol. 81: 329-369, 2003.
Sakaguchi, S. Control of immune responses by naturally arising CD4+ regulatory T cells. J. Exp. Med. 197: 397-401, 2003
Hori, S., Nomura, T., and Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 299: 1057-1061, 2003.
Wood, K. and Sakaguchi, S. Regulatory T cells in transplantation. Nat. Rev. Immunol. 3: 199-210, 2003.
Sakaguchi, S. Regulatory T cells: mediating compromises between host and parasite. Nat Immunol. 4: 10-11, 2003.
Takahashi, T., and Sakaguchi, S. The role of regulatory T cells in controlling immunologic self-tolerance. Int. Rev. Cytol. 225: 1-32, 2003.

Prize

2003Mochida Science Award
2004Cancer Research Institute's William B. Coley Award for Basic Immunology and Tumor Immunology
2005Takeda Medical Award
2005Takamine Memorial Sankyo Award
2007The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology
2008Uehara Memorial Award
2008The Keio Medical Science Prize
2009The Emperor's Purple Ribbon Medal
2012Asahi prize
2012The Japan Academy
2012Foreign Associate of NAS, USA
2015Maharshi Sushruta Award
2015Gairdner International Award
2015Chunichi Award
2017The Crafoord Prize

Special mention

Editorial Board
Science (Reviewing Editor)
Journal of Experimental Medicine (Advisory Editor)
Immunity (Editorial Board)
Immunological Reviews (Editorial Board)
International Immunology (Advisory Editor)
Journal of Experimental Pathology (Advisory Editor)
Cancer Immunity (Associate Editor)
eLife (Editorial Board)