{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Klicznik MM"],"funding":["Austrian Science Fund FWF","NIAID NIH HHS"],"pagination":["11164"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7341892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγ<sup>null</sup> (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69<sup>+</sup> memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69<sup>-</sup> T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases."],"journal":["Scientific reports"],"pubmed_title":["A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin."],"pmcid":["PMC7341892"],"funding_grant_id":["W 1213","R01 AI127726"],"pubmed_authors":["Benedetti A","Laimer M","Neuper T","Stoecklinger A","Klicznik MM","Holly R","Horejs-Hoeck J","Varkhande SR","Rosenblum MD","Reitsamer R","Campbell DJ","Murauer EM","Gratz IK","Gail LM","Sir A"],"additional_accession":[]},"is_claimable":false,"name":"A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin.","description":"Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγ<sup>null</sup> (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69<sup>+</sup> memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69<sup>-</sup> T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2024-11-06T11:31:40.023Z","creation":"2024-11-06T11:31:40.023Z"},"accession":"S-EPMC7341892","cross_references":{"pubmed":["32636404"],"doi":["10.1038/s41598-020-67430-7"]}}