Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Curr Protoc ; 4(8): e1113, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39105684

RESUMEN

Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.


Asunto(s)
Alopecia Areata , Modelos Animales de Enfermedad , Ratones Endogámicos C3H , Trasplante de Piel , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/patología , Alopecia Areata/inmunología , Animales , Ratones , Femenino , Masculino , Traslado Adoptivo
2.
PNAS Nexus ; 1(3): pgac111, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35899069

RESUMEN

The primary forms of cicatricial (scarring) alopecia (PCA) are a group of inflammatory, irreversible hair loss disorders characterized by immune cell infiltrates targeting hair follicles (HFs). Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and centrifugal cicatricial alopecia (CCCA) are among the main subtypes of PCAs. The pathogenesis of the different types of PCAs are poorly understood, and current treatment regimens yield inconsistent and unsatisfactory results. We performed high-throughput RNA-sequencing on scalp biopsies of a large cohort PCA patients to develop gene expression-based signatures, trained into machine-learning-based predictive models and pathways associated with dysregulated gene expression. We performed morphological and cytokine analysis to define the immune cell populations found in PCA subtypes. We identified a common PCA gene signature that was shared between LPP, FFA, and CCCA, which revealed a significant over-representation of mast cell (MC) genes, as well as downregulation of cholesterogenic pathways and upregulation of fibrosis and immune signaling genes. Immunohistological analyses revealed an increased presence of MCs in PCAs lesions. Our gene expression analyses revealed common pathways associated with PCAs, with a strong association with MCs. The indistinguishable differences in gene expression profiles and immune cell signatures between LPP, FFA, and CCCA suggest that similar treatment regimens may be effective in treating these irreversible forms of hair loss.

3.
Methods Mol Biol ; 2154: 121-131, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32314212

RESUMEN

Surgical induction of alopecia areata (AA) via full-thickness grafting of spontaneous AA-affected C3H/HeJ mouse skin to naïve recipients has been a primary method of transferring the AA disease model phenotype. However, this method is associated with the need to perform an invasive procedure that could negatively impact animal wellbeing. Therefore, a rodent model that rapidly develops AA at a predictable rate and without the need to perform invasive surgical procedures on the mice is essential for studying the pathogenesis of AA. Here we describe a cell injection technique using cultured skin-draining lymph node cells (LNCs) injected intradermally into naïve recipients to induce rapid AA development. The cultured LNCs can reach ~ten fold expansion after 6 days with specific cytokine stimulation. The LNCs derived from a single AA affected mouse donor can induce AA development in more than 80 naïve mice within 2-18 weeks. For comparative control studies, mice receiving cultured LNCs from normal donors remain normally haired. The method enables the production of large numbers of AA mice for use in research and treatment development studies while avoiding the use of surgical procedures. We anticipate that the protocol can also be adapted for use in other mouse autoimmune disease models.


Asunto(s)
Traslado Adoptivo , Alopecia Areata/etiología , Alopecia Areata/metabolismo , Linfocitos/metabolismo , Traslado Adoptivo/métodos , Alopecia Areata/patología , Animales , Técnicas de Cultivo de Célula , Separación Celular/métodos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Ganglios Linfáticos , Activación de Linfocitos , Linfocitos/citología , Linfocitos/inmunología , Ratones , Ratones Endogámicos C3H , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
4.
J Invest Dermatol ; 138(9): 1911-1916, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30057345

RESUMEN

The advancement of genetic and preclinical studies has uncovered the mechanisms involved in the pathogenesis of alopecia areata (AA). The development of targeted therapies using small molecules blocking specific pathways for the treatment of AA is underway. By repurposing Food and Drug Administration-approved small molecule JAK inhibitors as treatments for AA, it has been demonstrated that JAK inhibitors can effectively reverse hair loss in patients with moderate to severe AA. In this review, we summarize and discuss the current preclinical and clinical studies on JAK inhibitors, as well as the prospects of using JAK inhibitors for the treatment of AA.


Asunto(s)
Alopecia Areata/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Quinasas Janus/antagonistas & inhibidores , Alopecia Areata/metabolismo , Animales , Humanos
5.
J Invest Dermatol ; 136(8): 1617-1626, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27094591

RESUMEN

Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.


Asunto(s)
Alopecia Areata/sangre , Alopecia Areata/inmunología , Autoantígenos/inmunología , Epítopos/inmunología , Adulto , Anciano , Algoritmos , Apoptosis , Medios de Cultivo Condicionados/química , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Antígeno HLA-A2/metabolismo , Haplotipos , Humanos , Interferón gamma/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Queratinocitos/inmunología , Queratinocitos/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Melanocitos/inmunología , Melanocitos/metabolismo , Persona de Mediana Edad , Pronóstico , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA