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Albert Zlotnik

Publications and source records attributed to Albert Zlotnik.

22 records · Page 2Linked to original sources

CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.

The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.

Animals↗

Chemokines: agents for the immunotherapy of cancer?

Chemokines, a superfamily of small cytokine-like molecules, regulate leukocyte transport in the body. In recent years, we have witnessed the transition of immunotherapeutic strategies from the laboratory to the bedside. Here, we review the role of chemokines in tumour biology and the development of the host's anti-tumour defence. We summarize the current knowledge of chemokine-receptor expression by relevant cellular components of the immune system and the role of their ligands in the organization of the antitumour immune response. Finally, we discuss recent findings which indicate that chemokines have therapeutic potential as adjuvants or treatments in antitumour immunotherapy, as well as remaining questions and perspectives for translating experimental evidence into clinical practice.

Animals↗

Adenoviral-mediated gene transfer of lymphotactin to the lungs of mice and rats results in infiltration and direct accumulation of CD4+, CD8+, and NK cells.

Chemokines are small 8-12-kDa chemotactic cytokines that were initially characterized for their ability to control leukocyte trafficking and, to a lesser extent, leukocyte function. Lymphotactin was first described as a T lymphocyte-specific chemotactic factor. However, it has since been shown to also be a potent attractant for natural killer (NK) cells. The chemotactic properties of lymphotactin suggested from in vitro data prompted us to study the in vivo activity of this chemokine. We constructed an adenovirus vector expressing murine lymphotactin (Ad mLym) and used this construct to overexpress lymphotactin in the lungs of both mice and rats, with similar outcomes. In brief, the accumulation of CD4(+) and CD8(+) T cells and NK cells surprisingly demonstrated slow kinetics, uncharacteristic of the chemoattractant potential seen with other chemokines. Lymphocyte accumulation in the lung was not evident prior to 24 h after gene transfer and reached a peak by day 7 in mice and day 14 in rats. Interestingly, the cellular infiltrate recruited to the lung by lymphotactin was a heterogeneous mixture of lymphocytes, monocytes, and neutrophils. Administration of Ad mLym to BALB/c SCID mice demonstrated that the presence of monocytes and neutrophils in the bronchoalveolar lavage (BAL) of wild-type BALB/c mice was likely due to the action of lymphotactin on lymphocytes. These findings extend the previous in vitro findings on the activity of lymphotactin and provide a model for studying the local effects of overexpressing chemokines in various tissues in vivo.

Adenoviridae↗