期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 16, 页码 7443-7448出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0912943107
关键词
dendritic epidermal T cells; skin T cells; T cell trafficking
资金
- National Institutes of Health [R01 AI041707, R37 AI025082]
Dendritic epidermal T cells (DETC) express an invariant V gamma 3/V delta 1 T-cell receptor, appear in fetal epidermis, and forma population of resident epidermal T cells. Their temporal development in the thymus has been studied extensively. However, little is known about the mechanisms involved in the embryonic trafficking of DETC from thymus to epidermis. We demonstrate that DETC in adult skin, as well as the DETC precursors in fetal thymus, express E and P selectin ligands (E- and P-lig). Mice deficient in alpha 1,3 fucosyltransferases IV and VII (FTIV/VII) cannot synthesize the carbohydrate motifs that form key elements of these selectin ligands. The numbers of DETC in the epidermis of FTIV/VII-/- mice were dramatically reduced compared with normal mice. However, the development of DETC precursors in fetal thymus was identical in normal and FTIV/VII-/- mice, suggesting that the DETC precursors produced in FTIV/VII-/- mice could not traffic effectively to skin because they lack E- and P-lig. We tested this hypothesis by daily injection of blocking antibodies against E and P selectin into pregnant mice. Mice born from dams treated with anti-selectin antibodies, but not those born from dams treated with isotype control, had significantly diminished numbers of DETC. To test the role of chemokine receptors in DETC skin homing, we examined skin from CCR4(-/-) and CCR10(-/-) mice, respectively. DETC were significantly reduced in CCR4(-/-) mice but were present at normal levels in CCR10(-/-) mice. Our results present evidence for the crucial role of trafficking molecules in embryonic migration of DETC precursors to skin.
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