RESUMEN
Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-Hâdependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR. We observed an increase in viable S. aureus abundance on sites with increased severity of disease, and many virulence factors were expressed at the AD skin sites. Surprisingly, we did not observe any significant upregulation of the virulence factors at the lesional sites compared with those at the nonlesional control. Overall, we utilized a robust assay to directly detect and quantify viable S. aureus and its associated virulence factors at the site of AD skin lesions. This method can be extended to study the expression of skin microbial genes at the sites of various dermatological conditions.
RESUMEN
Telogen effluvium (TE) is a common cause of diffuse non-scarring hair loss that is usually precipitated by physiological stress such as childbirth or sudden weight loss. Despite its high rate of remission, this phenomenon of sudden excessive hair loss can be very worrisome and upsetting for affected individuals and may significantly impact their quality of life. Due to the multifactorial causes and precipitants of TE, it is often challenging to diagnose and manage. Further, the mechanisms through which physiological stress influences the human hair cycle is unknown, and there are no targeted treatments for the management of TE. This review will describe the approach in making a diagnosis of TE, summarize the latest developments made in understanding the mechanisms of TE, outline the treatments tried, and recommend ways for advancing the study of this dermatological condition.
Asunto(s)
Alopecia Areata/etiología , Ansiedad/terapia , Folículo Piloso/crecimiento & desarrollo , Estrés Psicológico/terapia , Administración Oral , Administración Tópica , Alopecia Areata/diagnóstico , Alopecia Areata/psicología , Alopecia Areata/terapia , Ansiedad/complicaciones , Ansiedad/psicología , Apoptosis/efectos de los fármacos , Biopsia , Terapia Combinada/métodos , Consejo , Diagnóstico Diferencial , Suplementos Dietéticos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/patología , Humanos , Minoxidil/administración & dosificación , Educación del Paciente como Asunto/métodos , Extractos Vegetales/administración & dosificación , Calidad de Vida , Estrés Psicológico/complicaciones , Estrés Psicológico/psicología , Vitamina D/administración & dosificaciónRESUMEN
Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease.
Asunto(s)
Tipificación del Cuerpo , Proteínas Morfogenéticas Óseas/metabolismo , Embrión no Mamífero/embriología , Glicoproteínas de Membrana/metabolismo , Vía de Señalización Wnt , Proteínas de Xenopus/metabolismo , Animales , Proteínas Morfogenéticas Óseas/genética , Glicoproteínas de Membrana/genética , Dominios Proteicos , Proteínas de Xenopus/genética , Xenopus laevisRESUMEN
The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.
Asunto(s)
Cabello/inmunología , Cabello/fisiología , Sistema Inmunológico/fisiología , Alopecia/inmunología , Alopecia/fisiopatología , Alopecia Areata/inmunología , Alopecia Areata/fisiopatología , Animales , Biopsia , Ciclo Celular , Transición Epitelial-Mesenquimal , Folículo Piloso/citología , Homeostasis , Humanos , Ratones , Piel/inmunología , Fenómenos Fisiológicos de la PielRESUMEN
Hair growth can be induced from resting mouse hair follicles by topical application of JAK inhibitors, suggesting that JAK-STAT signaling is required for maintaining hair follicle stem cells (HFSCs) in a quiescent state. Here, we show that Oncostatin M (OSM), an IL-6 family cytokine, negatively regulates hair growth by signaling through JAK-STAT5 to maintain HFSC quiescence. Genetic deletion of the OSM receptor or STAT5 can induce premature HFSC activation, suggesting that the resting telogen stage is actively maintained by the hair follicle niche. Single-cell RNA sequencing revealed that the OSM source is not intrinsic to the hair follicle itself and is instead a subset of TREM2+ macrophages that is enriched within the resting follicle and deceases immediately prior to HFSC activation. In vivo inhibition of macrophage function was sufficient to induce HFSC proliferation and hair cycle induction. Together these results clarify how JAK-STAT signaling actively inhibits hair growth.
Asunto(s)
Folículo Piloso/citología , Cabello/crecimiento & desarrollo , Macrófagos/metabolismo , Oncostatina M/metabolismo , Células Madre/citología , Animales , Ciclo Celular , Proliferación Celular , Dermis/citología , Dermis/metabolismo , Femenino , Folículo Piloso/metabolismo , Humanos , Janus Quinasa 2/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores Inmunológicos/metabolismo , Factor de Transcripción STAT5/metabolismo , Transducción de Señal , Células Madre/metabolismoRESUMEN
Treatments for alopecia areata (AA) have evolved over the decades from broad and nonspecific therapies to those that are now more targeted and rationally selected. This was achieved by means of close cooperation and communication between clinicians and basic scientists, which resulted in the elucidation and understanding of the unique pathophysiology of AA. In this review we discuss this evolution and how novel therapies for AA have changed over the decades, what we have in our current arsenal of drugs for this potentially devastating disease, and what the future holds.
Asunto(s)
Alopecia Areata/tratamiento farmacológico , Alopecia Areata/fisiopatología , Desarrollo de Medicamentos , Alopecia Areata/epidemiología , Alopecia Areata/inmunología , HumanosRESUMEN
Recent genetic and preclinical studies have increased our understanding of the immunopathogenesis of alopecia areata (AA). This has allowed expedited development of targeted therapies for the treatment of AA, and a paradigm shift in our approach and understanding of autoimmunity and the hair follicle. The synergy between preclinical studies, animal models, and translational studies has led to unprecedented advances in the treatment options for AA, ultimately benefiting patients who have had little recourse. In this review, we summarize the scientific field of contemporary AA research, and look forward to potential new technologies and developments.
Asunto(s)
Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Inmunosupresores/uso terapéutico , Animales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Investigación Biomédica TraslacionalRESUMEN
BACKGROUND: Morphologically and histopathologically, drug- and non-drug-induced maculopapular rashes can be almost indistinguishable. It has been postulated that Fas-ligand (Fas-L) is involved in the pathogenesis of drug rashes but not in the genesis of rashes, such as viral exanthems, that are not induced by medications. AIM: This study sought to determine if epidermal Fas-L is a distinguishing feature in the pathology of drug and non-drug maculopapular rashes. METHODS: Archived skin biopsies of patients with a confirmed diagnosis of drug or non-drug maculopapular rashes (n = 10 each) and positive and negative controls were retrieved for immunohistochemical staining for Fas-L. The proportion of Fas-L-positive skin biopsies were compared. The presence of tissue eosinophilia was also evaluated. RESULTS: Ten percent of non-drug-induced rashes were Fas-L positive compared to 50% of drug rashes (p = 0.05). Twenty percent of non-drug exanthems had moderate tissue eosinophilia, while 60% from drug rashes had moderate to dense tissue eosinophilia (p = 0.17). CONCLUSION: There is a trend toward Fas-L being more prevalent in the epidermis of drug maculopapular rashes, although this did not reach statistical significance. This is possibly because of the small sample size.