A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin
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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 null (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 + memory T cells produced higher levels of effector cytokines in response to Candida albicans , compared to CD69 - T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.
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The mouse is a standard model for investigating skin development and disease in vivo.
“The mouse is a standard model for investigating skin development and disease in vivo”
From Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells (2022) · cites this paper as [13]
The Introduction says skin-humanized mice are used to study human inflammatory skin conditions in vivo, supporting the disease portion. It does not establish that mice are a standard model for investigating skin development; the model described here is specifically designed to study human cutaneous T cells. (LLM, conf=0.85)
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Tissue-Resident Memory T Cells in Skin Diseases: A Systematic Review
Emmanuel, T., Mistegård, J., Bregnhøj, A., Johansen, C., & Iversen, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22169004 · Cited by 28 · see citing works
“Three studies explored infection with the commensal fungus Candida albicans and showed that Candida albicans can generate long-lived protective CD4+ TRMs in the skin [112]; in particular, the CD4+ CD69+ TRM-like T cells showed increased effector function in response to Candida albicans [54].”
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- Authors
- Klicznik, M. M., Benedetti, A., Gail, L. M., Varkhande, S. R., Holly, R., Laimer, M., Stoecklinger, A., Sir, A., Reitsamer, R., Neuper, T., Horejs-Hoeck, J., Rosenblum, M. D., Campbell, D. J., Murauer, E. M., & Gratz, I. K.
- Affiliations
- University of Salzburg (AT)
- Paracelsus Medical University (AT)
- University of California, San Francisco (US)
- University of Washington (US)
- Corresponding author
- Gratz, Iris K.
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-07-07
- Volume
- 10
- Issue
- 1
- Pages
- 11164-11164
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7341892
- OpenAlex
- W3039937420
- Semantic Scholar
- c1e68858f864643892cacf87d7e51ab70418a013
- Cited by
- 20
- References
- 82
- Citations by year
- 2026: 4 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 4
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Dystrophic Epidermolysis Bullosa Research Association
- Österreichischen Akademie der Wissenschaften
- Austrian Science Fund (W1213)
- Universität Salzburg
- Paracelsus Medizinische Privatuniversität
- DEBRA Austria
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI127726)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- humanized mice, NSG mice, T cell recruitment, tissue-resident memory T cells, CD69, Candida albicans, skin immunology, immune-mediated skin disease
- MeSH terms
- Adult, Animals, Candida albicans, Female, Humans, Immunologic Memory, Male, Middle Aged, Skin, T-Lymphocytes, CD4-Positive T-Lymphocytes, Skin Transplantation, Mice, Inbred NOD, Tissue Engineering, Mice, Heterografts
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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