Innsbruck, Austria
Innsbruck, Austria

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Dubrac S.,Innsbruck Medical University | Schmuth M.,Innsbruck Medical University | Ebner S.,Innsbruck Medical University | Ebner S.,K1 Center Oncotyrol
Immunology and Cell Biology | Year: 2010

The manifestation of atopic dermatitis (AD) results from a complex interaction of environmental factors, skin barrier defects and immunological phenomena. The initial events in AD remain unclear while much progress has been made in identifying the mechanisms leading to the manifestation and maintenance of allergic inflammation. AD pathogenesis can be approached from many different points of view. In this review, we describe findings in mouse models and in humans separately. We focus on recent findings that underscore the importance of Langerhans cells in initial mechanisms of skin inflammation in AD. © 2010 Australasian Society for Immunology Inc.

Nguyen V.A.,Innsbruck Medical University | Dubrac S.,Innsbruck Medical University | Forstner M.,Innsbruck Medical University | Forstner M.,K1 Center Oncotyrol | And 6 more authors.
Journal of Cellular and Molecular Medicine | Year: 2011

Thymic stromal lymphopoietin (TSLP) endows human blood-derived CD11c + dendritic cells (DCs) and Langerhans cells (LCs) obtained from human epidermis with the capacity to induce pro-allergic T cells. In this study, we investigated the effect of TSLP on umbilical cord blood CD34 +-derived LC-like cells. These cells are often used as model cells for LCs obtained from epidermis. Under the influence of TSLP, both cell types differed in several ways. As defined by CD83, CD80 and CD86, TSLP did not increase maturation of LC-like cells when compared with freshly isolated LCs and epidermal émigrés. Differences were also found in the production of chemokine (C-C motif) ligand (CCL)17. LCs made this chemokine only when primed by TSLP and further stimulated by CD40 ligation. In contrast, LC-like cells released CCL17 in response to CD40 ligation, irrespective of a prior treatment with TSLP. Moreover, the CCL17 levels secreted by LC-like cells were at least five times higher than those from migratory LCs. After maturation with a cytokine cocktail consisting of tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and prostaglandin (PG)E 2 LC-like cells released IL-12p70 in response to CD40 ligation. Most importantly and in contrast to LC, TSLP-treated LC-like cells did not induce a pro-allergic cytokine pattern in helper T cells. Due to their different cytokine secretion and the different cytokine production they induce in naïve T cells, we conclude that one has to be cautious to take LC-like cells as a paradigm for 'real' LCs from the epidermis. © 2011 The Authors Journal compilation © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Thurnher M.,Innsbruck Medical University | Thurnher M.,K1 Center Oncotyrol | Gruenbacher G.,Innsbruck Medical University | Gruenbacher G.,K1 Center Oncotyrol | And 2 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2013

The mevalonate pathway is a highly conserved metabolic cascade and provides isoprenoid building blocks for the biosynthesis of vital cellular products such as cholesterol or prenyl pyrophosphates that serve as substrates for the posttranslational prenylation of numerous proteins. The pathway, which is frequently hyperactive in cancer cells, is considered an important target in cancer therapy, since prenylated members of the Ras superfamily are crucially involved in the control of proliferation, survival, invasion and metastasis of tumour cells. Upstream accumulation and downstream depletion of mevalonate pathway intermediates as induced for instance by aminobisphosphonates translate into different effects in cancer and immune cells. Thus, mevalonate pathway regulation can affect tumour biology either directly or exhibit indirect antitumour effects through stimulating cancer immune surveillance. The present review summarizes major effects of pharmacologic mevalonate pathway regulation in cancer and immune cells that may collaboratively contribute to the efficacy of cancer therapy. © 2013 Elsevier B.V.

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