NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype

Abstract

NOD/Scid IL2Rγnull (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMC) donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine if these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from AD and PV patients were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of AD and PV patients with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network.Following dermal application of DMSO, both NSG-AD and NSG-PV mice exhibited increased clinical, skin and histological scores. Immuno-histochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLPR-expressing monocytes, switched B cells and MCP-3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD and NSG-PV mice differ and partially reflect the respective human disease.