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      Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

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          Abstract

          The success of topically applied treatments on skin relies on the efficacy of skin penetration. In order to increase particle or product penetration, mild skin barrier disruption methods can be used. We previously described cyanoacrylate skin surface stripping as an efficient method to open hair follicles, enhance particle penetration, and activate Langerhans cells. We conducted ex vivo and in vivo measurements on human skin to characterize the biological effect and quantify barrier disruption-related inflammation on a molecular level. Despite the known immunostimulatory effects, this barrier disruption and hair follicle opening method was well accepted and did not result in lasting changes of skin physiological parameters, cytokine production, or clinical side effects. Only in ex vivo human skin did we find a discrete increase in IP-10, TGF-β, IL-8, and GM-CSF mRNA. The data underline the safety profile of this method and demonstrate that the procedure per se does not cause substantial inflammation or skin damage, which is also of interest when applied to non-invasive sampling of biomarkers in clinical trials.

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          Most cited references32

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          Immune surveillance in the skin: mechanisms and clinical consequences

          Key Points The skin, together with other epithelial-cell interfaces with a hostile environment, supports a range of passive and active immune defence mechanisms. Cutaneous immune responses serve as a model for the study of interactions between innate and acquired immune mechanisms. Adaptive immune surveillance addresses the logistical challenge of targeting naive, effector and memory T cells to their respective sites of function by using distinct homing mechanisms at different stages of the immune response, termed primary, secondary and tertiary immune surveillance. Primary immune surveillance involves the process by which tissue dendritic cells are induced to engulf foreign particles, undergo maturation and emigrate through the afferent lymphatics to the local draining lymph node, where they encounter naive T cells recruited from the peripheral circulation. This greatly increases the efficiency with which naive T cells are exposed to antigens presented by professional antigen-presenting cells. Secondary immune surveillance involves the production and distribution of antigen-specific effector memory T cells that express homing receptors that direct their migration back to the tissue draining the lymph node where activation occurred and their participation in tissue-based immune responses. The persistence of memory T cells with both antigen and tissue specificity also protects against possible future encounters with the same pathogen, by providing a population of antigen-specific effector cells pre-targeted to the site where exposure to that pathogen might most probably recur. Tertiary immune surveillance involves the production of central memory and effector cells potentially directed to lymph nodes and tissues other than the site of primary exposure, providing broad coverage in the event that the pathogen is encountered through a different route. These concepts have implications for the understanding of both inflammatory skin disorders and the development of antitumour and antipathogen vaccine strategies.
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            CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells.

            CD8(+) T cells play a critical role in limiting peripheral virus replication, yet how they locate virus-infected cells within tissues is unknown. Here, we have examined the environmental signals that CD8(+) T cells use to localize and eliminate virus-infected skin cells. Epicutaneous vaccinia virus (VV) infection, mimicking human smallpox vaccination, greatly increased expression of the CXCR3 chemokine receptor ligands CXCL9 and CXCL10 in VV-infected skin. Despite normal T cell numbers in the skin, Cxcr3(-/-) mice exhibited dramatically impaired CD8(+)-T-cell-dependent virus clearance. Intravital microscopy revealed that Cxcr3(-/-) T cells were markedly deficient in locating, engaging, and killing virus-infected cells. Further, transfer of wild-type CD8(+) T cells restored viral clearance in Cxcr3(-/-) animals. These findings demonstrate a function for CXCR3 in enhancing the ability of tissue-localized CD8(+) T cells to locate virus-infected cells and thereby exert anti-viral effector functions.
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              Intradermal, epidermal and transcutaneous vaccination: from immunology to clinical practice.

              The dermis and epidermis are alternative sites for prophylactic vaccination that have received renewed interest in recent years, not only because of the ease of access to the skin, but also its unique immunological properties. This review discusses the characteristics of the skin, current knowledge on skin immunity and clinical experience with cutaneous immunization against infectious diseases, with a special focus on intradermal immunization. The most widely accepted paradigm explaining the efficacy of cutaneous immunization is reviewed and recent research suggesting where this paradigm may need some refinement is highlighted. Clinical investigations that have concentrated on the intradermal route to vaccinate against influenza, rabies or hepatitis B support the current knowledge on skin immunity and, when combined with recent progress made in the development of user-friendly injection systems, have stimulated the ongoing clinical development of novel vaccines.
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                Author and article information

                Journal
                SPP
                Skin Pharmacol Physiol
                10.1159/issn.1660-5527
                Skin Pharmacology and Physiology
                S. Karger AG
                1660-5527
                1660-5535
                2018
                May 2018
                07 March 2018
                : 31
                : 3
                : 115-124
                Affiliations
                aCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Berlin, Germany; bCentre d'Immunologie et des Maladies Infectieuses - Paris (Cimi-Paris), Sorbonne Universités UPMC, Université Paris 06 UMRS CR7, Inserm U1135, CNRS ERL 8255, Paris, France
                Author notes
                *Annika Vogt, Charité - Universitätsmedizin Berlin, Charitéplatz 1, DE-10117 Berlin (Germany), E-Mail annika.vogt@charite.de
                Article
                484443 Skin Pharmacol Physiol 2018;31:115–124
                10.1159/000484443
                29510378
                6c858934-7887-48bf-a964-343134b33c63
                © 2018 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 27 June 2017
                : 19 October 2017
                Page count
                Figures: 5, References: 42, Pages: 10
                Categories
                Original Paper

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Skin barrier,Particle penetration,Transcutaneous vaccination,Cyanoacrylate skin surface stripping,Tape stripping

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