Immune cells including T cells and antigen-presenting dendritic cells (DCs) migrate to and from the skin as part of the normal processes of immune surveillance and protection. Chemokines comprise a large family of protein that are intimately involved in recruiting these immune cells into peripheral tissues such as skin and in compartmentalizing them in certain regions of secondary lymphoid organs such as lymph nodes (LN). Over the last year, we have shown that skin dendritic cells express the chemokine receptor CXCR5 as they mature. In vitro, skin DCs respond to the CXCR5 ligand, BLC, in chemotaxis assays. In vivo, skin DCs appear to be able to partially home to B cell areas of the LN. T cells migrate into skin during immune responses by first binding to microvascular endothelial cells in the skin. Using a system comprised of cultured human dermal microvascular endothelial cells (HDMEC), we have shown that HDMEC strongly express message for a CCR6-ligand termed LARC. Interestingly, a discrete subset of skin-homing T cells express CCR6. Using a parallel plate flow chamber system, we have demonstrated that CCR6 appears to be critical for the firm adherence of memory T cells to activated HDMEC under physiologic flow conditions. Finally, we have shown that mast cells express CX3CR1, a receptor for the unique membrane-bound chemokine termed fractalkine. In vitro, mast cells respond to fractalkine in chemotaxis assays but are not stimulated to release preformed mediators. By immunohistochemical techniques, we have shown expression of fractalkine in populations of cells in skin where mast cells are known to accumulate. Thus, we have proposed that fractalkine participates in the anatomic localization of mast cells at immunologically critical sites of the skin including blood vessels and near dendritic cells.

Agency
National Institute of Health (NIH)
Institute
Division of Clinical Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010277-03
Application #
6433432
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chien, Andy J; Moore, Erin C; Lonsdorf, Anke S et al. (2009) Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci U S A 106:1193-8
Kakinuma, Takashi; Nadiminti, Hari; Lonsdorf, Anke S et al. (2007) Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location. Cancer Immunol Immunother 56:1119-31
Cardones, Adela R; Leitner, Wolfgang W; Fang, Lei et al. (2006) Genetic immunization with LYVE-1 cDNA yields function-blocking antibodies against native protein. Microvasc Res 71:32-9
Kakinuma, Takashi; Hwang, Sam T (2006) Chemokines, chemokine receptors, and cancer metastasis. J Leukoc Biol 79:639-51
Klebanoff, Christopher A; Gattinoni, Luca; Torabi-Parizi, Parizad et al. (2005) Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A 102:9571-6
Hwang, Sam T (2004) Chemokine receptors in melanoma: CCR9 has a potential role in metastasis to the small bowel. J Invest Dermatol 122:xiv-xv
Murakami, Takashi; Cardones, Adela R; Hwang, Sam T (2004) Chemokine receptors and melanoma metastasis. J Dermatol Sci 36:71-8
Sikder, Hashmat; Huso, David L; Zhang, Hong et al. (2003) Disruption of Id1 reveals major differences in angiogenesis between transplanted and autochthonous tumors. Cancer Cell 4:291-9
Yao, Lei; Salvucci, Ombretta; Cardones, Adela R et al. (2003) Selective expression of stromal-derived factor-1 in the capillary vascular endothelium plays a role in Kaposi sarcoma pathogenesis. Blood 102:3900-5
Murakami, Takashi; Cardones, Adela R; Finkelstein, Steven E et al. (2003) Immune evasion by murine melanoma mediated through CC chemokine receptor-10. J Exp Med 198:1337-47

Showing the most recent 10 out of 17 publications