Area of research
Immunology · Oncology
Research interest
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.
CTLA-4-expressing ILC3s restrain interleukin-23-mediated inflammation
Data from Two Distinct Mechanisms of Augmented Antitumor Activity by Modulation of Immunostimulatory/Inhibitory Signals
Data from Two Distinct Mechanisms of Augmented Antitumor Activity by Modulation of Immunostimulatory/Inhibitory Signals
Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells
CTLA-4 expression by B-1a B cells is essential for immune tolerance
Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction
Regulatory roles of IL-10–producing human follicular T cells
Functional Roles of the IgM Fc Receptor in the Immune System
Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity
Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation
Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization
T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow
Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4
Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood
Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations
Transient Ablation of Regulatory T cells Improves Antitumor Immunity in Colitis-Associated Colon Cancer
Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease
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.
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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
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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.
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Kitagawa Y, Ohkura N, Sakaguchi S. Epigenetic control of thymic Treg-cell development. Eur. J. Immunol. 2014 Oct 28.
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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
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Mikami N, Sakaguchi S. CD28 signals the differential control of regulatory T cells and effector T cells. Eur J Immunol. 44:955-957, 2014.
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Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nat Rev Rheumatol. 10:543-551 2014.
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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.
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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.
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Wing JB, Sakaguchi S. Foxp3+ Treg cells in humoral immunity. Int Immunol. 26: 61-69, 2014.
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Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 27: 1-7, 2014.
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Regulatory T cells: recommendations to simplify the nomenclature
The plasticity and stability of regulatory T cells