Abstract

We discovered and have characterized a unique T cell inhibitory pathway composed of DC-HIL on antigen presenting cells (APC) and its ligand syndecan- 4 (SD-4) on activated T cells. This pathway is distinguished by its ability to deactivate effector/memory T cells while sparing regulatory T cells. Our proposal will: elucidate signals within T cells triggered by DC-HIL/SD-4 ligation;develop strategies employing toxin-bearing DC-hIL to treat SD4+ T cell-mediated skin inflammation;and validate the differential effect of DC-HIL on effector vs. regulatory Tcells in vivo. Our new findings should lead to application of the DCHIL/ SD-4 pathway for biologic and/or pharmacologic benefit. Public

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI064927-05A1
Application #
7877448
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2009-07-15
Project End
2009-11-30
Budget Start
2009-07-15
Budget End
2009-11-30
Support Year
5
Fiscal Year
2009
Total Cost
$392,500
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Dermatology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Cao, Lauren Y; Chung, Jin-Sung; Teshima, Takahiro et al. (2016) Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell-Suppressor Mechanisms. J Invest Dermatol 136:1801-1810
Turrentine, Jake; Chung, Jin-Sung; Nezafati, Kaveh et al. (2014) DC-HIL+ CD14+ HLA-DR no/low cells are a potential blood marker and therapeutic target for melanoma. J Invest Dermatol 134:2839-2842
Chung, Jin-Sung; Tamura, Kyoichi; Akiyoshi, Hideo et al. (2014) The DC-HIL/syndecan-4 pathway regulates autoimmune responses through myeloid-derived suppressor cells. J Immunol 192:2576-84
Chung, Jin-Sung; Tamura, Kyoichi; Cruz Jr, Ponciano D et al. (2014) DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth. J Invest Dermatol 134:2784-2794
Chung, Jin-Sung; Tomihari, Mizuki; Tamura, Kyoichi et al. (2013) The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease. Immunology 138:173-82
Chung, Jin-Sung; Cruz Jr, Ponciano D; Ariizumi, Kiyoshi (2011) Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity. Eur J Immunol 41:1794-9
Chung, Jin-Sung; Shiue, Lisa H; Duvic, Madeleine et al. (2011) Sezary 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. Blood 117:3382-90
Tomihari, Mizuki; Chung, Jin-Sung; Akiyoshi, Hideo et al. (2010) DC-HIL/glycoprotein Nmb promotes growth of melanoma in mice by inhibiting the activation of tumor-reactive T cells. Cancer Res 70:5778-87
Akiyoshi, Hideo; Chung, Jin-Sung; Tomihari, Mizuki et al. (2010) 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. J Immunol 184:3554-61