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1.
Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy.
van Splunter, M, Liu, L, van Neerven, RJJ, Wichers, HJ, Hettinga, KA, de Jong, NW
Nutrients. 2020;(12)
Abstract
Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.
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2.
Histidine Metabolism and Function.
Brosnan, ME, Brosnan, JT
The Journal of nutrition. 2020;(Suppl 1):2570S-2575S
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Abstract
Histidine is a dietary essential amino acid because it cannot be synthesized in humans. The WHO/FAO requirement for adults for histidine is 10 mg · kg body weight-1 · d-1. Histidine is required for synthesis of proteins. It plays particularly important roles in the active site of enzymes, such as serine proteases (e.g., trypsin) where it is a member of the catalytic triad. Excess histidine may be converted to trans-urocanate by histidine ammonia lyase (histidase) in liver and skin. UV light in skin converts the trans form to cis-urocanate which plays an important protective role in skin. Liver is capable of complete catabolism of histidine by a pathway which requires folic acid for the last step, in which glutamate formiminotransferase converts the intermediate N-formiminoglutamate to glutamate, 5,10 methenyl-tetrahydrofolate, and ammonia. Inborn errors have been recognized in all of the catabolic enzymes of histidine. Histidine is required as a precursor of carnosine in human muscle and parts of the brain where carnosine appears to play an important role as a buffer and antioxidant. It is synthesized in the tissue by carnosine synthase from histidine and β-alanine, at the expense of ATP hydrolysis. Histidine can be decarboxylated to histamine by histidine decarboxylase. This reaction occurs in the enterochromaffin-like cells of the stomach, in the mast cells of the immune system, and in various regions of the brain where histamine may serve as a neurotransmitter.
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Potential of Skin Microbiome, Pro- and/or Pre-Biotics to Affect Local Cutaneous Responses to UV Exposure.
Patra, V, Gallais Sérézal, I, Wolf, P
Nutrients. 2020;(6)
Abstract
The human skin hosts innumerable microorganisms and maintains homeostasis with the local immune system despite the challenges offered by environmental factors such as ultraviolet radiation (UVR). UVR causes cutaneous alterations such as acute (i.e., sunburn) and chronic inflammation, tanning, photoaging, skin cancer, and immune modulation. Phototherapy on the other hand is widely used to treat inflammatory skin diseases such as psoriasis, atopic dermatitis, polymorphic light eruption and graft-versus-host disease (GvHD), as well as neoplastic skin diseases such as cutaneous T cell lymphoma, among others. Previous work has addressed the use of pro- and pre-biotics to protect against UVR through anti-oxidative, anti-inflammatory, anti-aging, anti-carcinogenic and/or pro-and contra-melanogenic properties. Herein, we discuss and share perspectives of the potential benefits of novel treatment strategies using microbes and pro- and pre-biotics as modulators of the skin response to UVR, and how they could act both for protection against UVR-induced skin damage and as enhancers of the UVR-driven therapeutic effects on the skin.
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How UV Light Touches the Brain and Endocrine System Through Skin, and Why.
Slominski, AT, Zmijewski, MA, Plonka, PM, Szaflarski, JP, Paus, R
Endocrinology. 2018;(5):1992-2007
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Abstract
The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain and restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine, and immune systems, all acting in concert to control body homeostasis. Although UV energy has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis but also induces skin pathology (e.g., cancer, aging, autoimmune responses). These effects are secondary to the transduction of UV electromagnetic energy into chemical, hormonal, and neural signals, defined by the nature of the chromophores and tissue compartments receiving specific UV wavelength. UV radiation can upregulate local neuroendocrine axes, with UVB being markedly more efficient than UVA. The locally induced cytokines, corticotropin-releasing hormone, urocortins, proopiomelanocortin-peptides, enkephalins, or others can be released into circulation to exert systemic effects, including activation of the central hypothalamic-pituitary-adrenal axis, opioidogenic effects, and immunosuppression, independent of vitamin D synthesis. Similar effects are seen after exposure of the eyes and skin to UV, through which UVB activates hypothalamic paraventricular and arcuate nuclei and exerts very rapid stimulatory effects on the brain. Thus, UV touches the brain and central neuroendocrine system to reset body homeostasis. This invites multiple therapeutic applications of UV radiation, for example, in the management of autoimmune and mood disorders, addiction, and obesity.
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The human skin microbiome.
Byrd, AL, Belkaid, Y, Segre, JA
Nature reviews. Microbiology. 2018;(3):143-155
Abstract
Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.
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Cutaneous and Mucosal Manifestations Associated with Celiac Disease.
Rodrigo, L, Beteta-Gorriti, V, Alvarez, N, Gómez de Castro, C, de Dios, A, Palacios, L, Santos-Juanes, J
Nutrients. 2018;(7)
Abstract
Celiac disease (CD) is an immune-mediated, gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, with dermatitis herpetiformis (DH) being the best characterized. These associated conditions may be the clue to reaching the diagnosis of CD. Over the last few years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in the absence of gastrointestinal symptoms, should give rise to an appropriate screening method for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated with CD and the possible mechanisms involved.
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Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin.
Edlich, A, Volz, P, Brodwolf, R, Unbehauen, M, Mundhenk, L, Gruber, AD, Hedtrich, S, Haag, R, Alexiev, U, Kleuser, B
Biomaterials. 2018;:60-70
Abstract
Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment.
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Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events.
Rimola, J, Díaz-González, Á, Darnell, A, Varela, M, Pons, F, Hernandez-Guerra, M, Delgado, M, Castroagudin, J, Matilla, A, Sangro, B, et al
Hepatology (Baltimore, Md.). 2018;(2):612-622
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Abstract
The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child-Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612-622).
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9.
[Not Available].
Lebaron, P, Bourrain, M
Annales de dermatologie et de venereologie. 2017;:S35-S41
Abstract
Human hosts a large number of microorganisms that constitute its microbiome and the vast majority of them are very useful and even essentials. The human microbiome is a complex ecosystem where live populations of transient or resident microorganisms. The process of co-development or co-adaptation played a major role in the establishment of indigenous communities and help explain the dominance of positive interactions (commensal, symbiotic or mutualistic) in the human-microorganism relationship. The assimilation of nutrients, production of anti-inflammatory compounds, defense against pathogens, vitamin production or stimulating the immune system are some of the key benefits of the indigenous microorganisms. Understanding the skin microbiome opens new exploratory fields and represents a real challenge for both the academic knowledge and the development of new therapeutic approaches.
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S100B: Correlation with Active Vitiligo Depigmentation.
Birlea, SA
The Journal of investigative dermatology. 2017;(7):1408-1410
Abstract
Vitiligo, the most common depigmenting disorder, is caused by immune destruction of melanocytes by cytotoxic CD8+ T cells. One weakness in vitiligo management is the lack of an assessment method for active depigmentation. Beginning with reports about increased S100B levels in different inflammatory and tissue damage processes, Speeckaert et al. explored correlations between the S100B dynamics and vitiligo activity, identifying high circulating S100B levels in patients with active depigmentation which were strongly correlated with the extent of affected skin surface. These authors have proposed S100B as a potential disease activity marker in vitiligo.