RESUMEN
Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel vector of which capsid was composed of capsid proteins derived from both of the AAV serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for AAV1 vector) and neuron specificity (for AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.
Asunto(s)
Dependovirus , Parvovirinae , Animales , Dependovirus/metabolismo , Transducción Genética , Vectores Genéticos/genética , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Transgenes , Primates/genética , Parvovirinae/genética , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Neuronas/metabolismoRESUMEN
BACKGROUND: The precise pathogenesis of alopecia areata remains unknown, although this disease seems to be triggered by helper T cell infiltration in hair follicles. Recent studies of psoriasis and vitiligo have demonstrated the involvement of Th17 cells. Psoriasis and vitiligo occasionally develop concomitantly or inversely in patients with alopecia areata. OBJECTIVE: The aim of this study was to determine whether Th17 cells are present in the affected lesions of alopecia areata. METHODS: We performed immunofluorescent staining of representative immunocompetent cells that had infiltrated into the skin of the scalp in 4 individuals with alopecia areata (single patchy alopecia areata, multiple patchy alopecia areata, alopecia totalis and alopecia universalis). RESULTS: We found the infiltration of CD4(+)IL-17A(+) Th17 cells in the dermis, particularly around hair follicles, in all 4 cases. CONCLUSIONS: These findings suggest the possibility that alopecia areata is induced by a Th17 cell-associated autoimmune mechanism.