Kiyoshi Ariizumi, Ph.D.

Immune responses need to be tightly regulated, particularly in the skin where the ability to defend against infections and cancers should be balanced.  This key process is heavily dependent on proper switching the differentiation program of myeloid cells between the immuno-stimulators and the immunosuppressors.  One-sided differentiation causes hyperactivation or immunosuppression, leading to autoimmune diseases (e.g., psoriasis on the skin) or promoting skin cancer growth, respectively.  We are studying molecular mechanisms through which myeloid cells (particularly, dendritic cells and macrophages) switch to the suppressors under the pathological conditions of psoriatic inflammation and melanoma, using mouse models (transgenic and gene-disrupted mice) and human clinical samples.  We are also thinking about translational studies to make the results of basic research applicable to the development of new treatments for these skin diseases.  

Graduate School

University of Tokyo - Japan (1985)

• Immune evasion by melanoma
• Inflammation-associated carcinogenesis
• Negative regulation of T cell-mediated immunity

Featured Publications

DC-HIL is a negative regulator of T cell activation.

Chung J-S, Sato K, Dougherty I, Cruz PD Jr, Ariizumi K. Blood Spring 2007 109 4320-4327

Cloning of a second dendritic Cell-associated C-type lectin (Dectin-2) and its alternatively spliced isoforms.

Ariizumi K, Shen G-L, Shikano S, Ritter RIII, Zukas P, Edelbaum D, Morita A, Takashima A. J Biol Chem 2000 275 11957-11963

Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity.

Chung JS, Cruz PD, Ariizumi K Eur. J. Immunol. 2011 Jun 41 6 1794-9

Sézary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface.

Chung JS, Shiue LH, Duvic M, Pandya A, Cruz PD, Ariizumi K Blood 2011 Mar 117 12 3382-90

DC-HIL/glycoprotein Nmb promotes growth of melanoma in mice by inhibiting the activation of tumor-reactive T cells.

Tomihari M, Chung JS, Akiyoshi H, Cruz PD, Ariizumi K Cancer Res. 2010 Jul 70 14 5778-87

Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: a new opportunity for treating activated T cell-driven disease.

Akiyoshi H, Chung JS, Tomihari M, Cruz PD, Ariizumi K J. Immunol. 2010 Apr 184 7 3554-61

Binding of DC-HIL to dermatophytic fungi induces tyrosine phosphorylation and potentiates antigen presenting cell function.

Chung JS, Yudate T, Tomihari M, Akiyoshi H, Cruz PD, Ariizumi K J. Immunol. 2009 Oct 183 8 5190-8

The DC-HIL/syndecan-4 pathway inhibits human allogeneic T-cell responses.

Chung JS, Bonkobara M, Tomihari M, Cruz PD, Ariizumi K Eur. J. Immunol. 2009 Apr 39 4 965-74

Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses.

Lopes L, Dewannieux M, Gileadi U, Bailey R, Ikeda Y, Whittaker C, Collin MP, Cerundolo V, Tomihari M, Ariizumi K, Collins MK J. Virol. 2008 Jan 82 1 86-95

Syndecan-4 mediates the co-inhibitory function of DC-HIL on T cell activation.

Chung J-S, Dougherty I, Cruz PD Jr, Ariizumi K. J. Immunol 2007 179 5778-5784

• Research career Development Award
  Awarded by the Dermatology Foundation (1994)
• Henry Christian Memorial Award
  Awarded by the American Federation for Clinical Research (1993)

• American Association of Immunologists
• Society for Investigative Dermatology