Development of AVATAR mouse for personalized medicine in patients with atopic dermatitis
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a complex pathogenesis, necessitating the development of personalized therapeutic approaches. In this study, we established a humanized mouse model, termed the AVATAR mouse, designed to replicate the immune responses observed in human AD patients. To achieve this, CD3+ T cells isolated from peripheral blood mononuclear cells (PBMCs) of AD patients were administered intravenously, while CD3-depleted PBMCs were injected intradermally as antigen-presenting cells (APCs) into immunodeficient mice. Following this, the mice were exposed to house dust mites (HDM) to induce AD-like immune responses. We then performed single-cell RNA sequencing on skin samples from HDM-sensitized and non-sensitized AVATAR mice, as well as from lesional and non-lesional skin of human AD patients, to investigate the role of specific dendritic cells (DCs) as APCs and to determine the profile of the T cell responses induced in the AVATAR model. The results revealed that, in HDM-sensitized AVATAR mice, there was an increase in IRF4+MRC1+ cDC2s and Th2-related gene expression, mirroring the findings observed in human AD lesional skin. These findings suggest that the AVATAR mouse model can replicate the immune responses seen in individual AD patients, providing a valuable platform for the study of personalized treatment strategies in atopic dermatitis.