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Frederick, MD, United States

Albanesi C.,Laboratory of Experimental Immunology
Current Opinion in Allergy and Clinical Immunology | Year: 2010

Purpose of review: The aim of the review is to provide up-to-date information on the multiple roles of epidermal keratinocytes in the immune reactions associated with allergic contact dermatitis and atopic dermatitis skin diseasesRecent findings: In the last two decades, it has become clear that keratinocytes are highly active immunological cells, with major control over the acute and the chronic phases of skin inflammation by means of cytokine/chemokine production and surface molecule expression. Keratinocyte responses in skin allergic reactions are rather disease-specific and keratinocytes from genetically determined skin disorders, including atopic dermatitis, show intrinsic abnormalities in their capacity to respond to trigger factors. Summary: Lymphokines and cytokines released by T lymphocytes and other immune cells represent the most important stimuli that elicit the inflammatory activation of keratinocytes. Depending on the type and extent of T-cell infiltrate present in allergic contact dermatitis and atopic dermatitis skin lesions, keratinocytes are exposed to different cytokine micromilieu and, in turn, produce flogosis mediators qualitatively and quantitatively specific for each disease. Keratinocyte-derived inflammatory molecules amplificate skin immune responses associated with allergic contact dermatitis and atopic dermatitis, and contribute to the disease process and clinical phenotype development. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Cavani A.,Laboratory of Experimental Immunology | Pennino D.,Helmholtz Center Munich | Eyerich K.,Helmholtz Center Munich
Chemical Immunology and Allergy | Year: 2012

Development of eczematous skin reactions depends on disease-specific and time-dependent recruitment of a variety of leukocytes affecting resident skin cells through cytotoxic mechanisms and release of cytokines. Th17 and Th22, defined as RORC+IL-17+ and IL-17-IFN-γ-IL-22+ cells, respectively, belong to a newly identified class of lymphocytes specifically involved in dialogue with non-immune cells. In line with this function, both Th17 and Th22 cells are enriched in many immune-mediated skin diseases, such as a topic dermatitis, allergic contact dermatitis and psoriasis. Both IL-17 and IL-22 activate keratinocyte innate immune defenses, thus protecting the skin from pathogen invasion. However, Th17 and Th22 differ in their proinflammatory functions, being prominent in the first T cell subset and occasional/opportunistic in the second T cell subset. Most of the proinflammatory functions of Th17 depend on the synergic activity of IFN-γ and IL-17 on target cells. Together with IFN-γ, IL-17 strongly enhances adhesion molecules on keratinocytes, thus promoting T cell-keratinocyte adhesion and T cell-mediated cytotoxicity, resulting in keratinocyte apoptosis. In contrast, Th22 cells guarantee skin integrity by inducing keratinocyte proliferation and migration. However, in inflamed skin, Th22 could contribute to the amplification of immune responses by enhancing the TNF-α-induced cytokines and chemokines released by keratinocytes. © 2012 S. Karger AG, Basel. Source

Albanesi C.,Laboratory of Experimental Immunology | Pastore S.,Dell
Current Drug Metabolism | Year: 2010

Inflammatory dermatoses encompass an enormous area of dermatopathology. These diseases are triggered and maintained by aberrant responses of the cells of the skin immune system. In the last decade it has become clear that epidermal keratinocytes are highly active immunological cells, with a major control over the acute and the chronic phase of skin inflammation by means of cytokine/ chemokine production and surface molecule expression. In their turn, these rather disease-specific events driven by keratinocytes lead to a rich inflammatory infiltrate in the whole skin including the upper layers of the epidermis, and eventually in the aggravation and/or perpetuation of the skin disorder. Recently introduced single molecule-targeted biological drugs are offering the best demonstration that a fine definition of the molecular pathways underlying skin disorders is now necessary to identify the relevant therapeutic targets and finally obtain successful treatment of these diseases. In this review, we will summarize recent progress in our understanding of the immunologic basis of psoriasis, allergic contact dermatitis and atopic dermatitis, with special emphasis on potentially effective targets for novel anti-inflammatory drugs. © 2010 Bentham Science Publishers Ltd. Source

Eyerich S.,Helmholtz Center Munich | Onken A.T.,TU Munich | Weidinger S.,University of Kiel | Franke A.,University of Kiel | And 10 more authors.
New England Journal of Medicine | Year: 2011

The simultaneous occurrence of psoriasis driven by type 1 helper T (Th1) cells and type 17 helper T (Th17) cells and atopic eczema dominated by type 2 helper T (Th2) cells is rare. Here, we describe three patients with co-occurring psoriasis and atopic eczema with an antagonistic course and distinct T-cell infiltrates in lesions from psoriasis and those from atopic eczema. Sensitized patients with psoriasis had a reaction to epicutaneous allergen challenge, with clinically and histologically verified eczema lesions containing a large number of allergen-reactive T cells. These findings support a causative role for T cells triggered by specific antigens in both psoriasis and atopic eczema. Copyright © 2011 Massachusetts Medical Society. Source

Moitra K.,Laboratory of Experimental Immunology | Lou H.,SAIC | Dean M.,Laboratory of Experimental Immunology
Clinical Pharmacology and Therapeutics | Year: 2011

Stem cells possess the dual properties of self-renewal and pluripotency. Self-renewal affords these populations the luxury of self-propagation, whereas pluripotency allows them to produce the multitude of cell types found in the body. Protection of the stem cell population from damage or death is critical because these cells need to remain intact throughout the life of an organism. The principal mechanism of protection is through expression of multifunctional efflux transportersthe adenosine triphosphate-binding cassette (ABC) transporters that are the guardians of the stem cell population. Ironically, it has been shown that these ABC efflux pumps also afford protection to cancer stem cells (CSCs), shielding them from the adverse effects of chemotherapeutic insult. It is therefore imperative to gain a better understanding of the mechanisms involved in the resistance of stem cells to chemotherapy, which could lead to the discovery of new therapeutic targets and improvement of current anticancer strategies. © 2011 ASCPT. Source

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