Laboratory for Immune Homeostasis

The immune system has evolved the ability to distinguish "self" from "non-self" to maintain homeostasis of the body. The immunological "self" is determined partly by genetic factors but develops and changes in an adaptive and acquired manner, relying on interactions with changing internal as well as external environments. The ultimate goal of this laboratory is to elucidate the basic principle that governs the development of such immunological "self" throughout multiple layers, from genes, molecules, cells, cell populations, tissues, through individuals. Towards this end, we focus on a cell-extrinsic, dominant control mechanism of immune responses that depends on a subpopulation of T lymphocytes called regulatory T cells. As one approach, we elucidate how mutations in the Foxp3 gene, encoding a transcription factor critical for regulatory T cell development and function, lead to a breakdown of the whole system and to the development of fatal autoimmune disease.

Research Fields

Biology & Biochemistry / Molecular Biology & Genetics / Immunology / Pharmacology & Toxicology / Multidisciplinary

Research Subjects

• Mechanisms of immunological tolerance and immune homeostasis
• Molecular basis of regulatory T cell development and function
• Mechanisms of T cell repertoire formation

Publications

1. Miyao T, Floess S, Setoguchi R, Luche H, Fehling HJ, Waldmann H, Huehn J, Hori S.:
   "Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells"
   Immunity 36(2): 262-275 (2012)
2. Hori S.:
   "Stability of regulatory T-cell lineage"
   Advances in Immunology 112: 1-24 (2011)
3. Kendal AR, Chen Y, Regateiro FS, Ma JB, Adams E, Cobbold SP, Hori S, Waldmann H.:
   "Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance"
   Journal of Experimental Medicine 208(10): 2043-2053 (2011)
4. Hori S.:
   "Regulatory T cell plasticity: beyond the controversies"
   Trends in Immunology 32(7): 295-300 (2011)
5. Hori S.:
   "Developmental plasticity of Foxp3+ regulatory T cells."
   Curr Opin Immunol 22(5): 575-582 (2010)
6. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S*, Fagarasan S* (corresponding and senior authors).:
   "Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches."
   Science 323(5920): 1488-1492 (2009)
7. Komatsu N, Mariotti-Ferrandiz ME, Wang Y, Malissen B, Waldmann H, Hori S.:
   "Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity."
   Proc Natl Acad Sci USA 106(6):1903-1908 (2009)
8. Komatsu N, Hori S.:
   "Full restoration of peripheral Foxp3+ regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras."
   Proc Natl Acad Sci USA 104(21): 8959-8964 (2007)
9. Setoguchi R, Hori S, Takahashi T, 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(5): 723-735 (2005)
10. Hori S, Nomura T, Sakaguchi S.:
    "Control of regulatory T cell development by the transcription factor Foxp3."
    Sciene 299(5609): 1057-1061 (2003)