Local heroes or villains: tissue-resident memory T cells in human health and disease
Open accessAbstract
Tissue-resident memory T (T RM) cells are increasingly associated with the outcomes of health and disease. T RM cells can mediate local immune protection against infections and cancer, which has led to interest in T RM cells as targets for vaccination and immunotherapies. However, these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis, alopecia areata, and vitiligo. Here, we summarize the biology of T RM cells established in animal models and in translational human studies. We review the beneficial effects of T RM cells in mediating protective responses against infection and cancer and the adverse role of T RM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of T RM cell activity is essential for the safe design of strategies that manipulate T RM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic T RM cells can be eliminated without losing local immunity.
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In organs other than the heart, TRM cells have been incriminated as key drivers of autoimmune diseases including psoriasis, vitiligo, type 1 diabetes, idiopathic arthritis, Alzheimer disease, and multiple sclerosis.
“Moreover, in other organs than the heart, T RM cells have been incriminated as key drivers of autoimmune diseases including psoriasis, vitiligo, type 1 diabetes, idiopathic arthritis, Alzheimer disease, and multiple sclerosis. 294,302-310”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [294]
The 'T RM CELLS IN AUTOIMMUNITY' section implicates tissue-resident memory T cells in multiple sclerosis and type 1 diabetes, and the skin-disease sections discuss their possible pathogenic roles in psoriasis and vitiligo. The source does not establish that they are key drivers of all these diseases: it says their direct contribution to psoriasis exacerbation is unknown. Our copy also does not address idiopathic arthritis or Alzheimer disease. Page numbers were not available in the supplied passages. (LLM, conf=0.89)
Experimental — accuracy not yet measuredTRM cells can be distinguished from effector memory T cells by downregulation of S1PR1 and upregulation of tissue retention molecules like CD103 and CD69.
“T RM cells can be distinguished from effector memory T cells by their downregulation of tissue egress protein S1PR1 (sphingosine 1-phosphate receptor) and upregulation of tissue retention molecules like CD103 and CD69. 292-294”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [294]
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- Authors
- Sasson, S. C., Gordon, C. L., Christo, S. N., Klenerman, P., & Mackay, L. K.
- Affiliations
- University of Oxford (GB)
- The University of Melbourne (AU)
- Corresponding author
- Klenerman, P.
- Mackay, L. K.
- Venue
- Cellular & Molecular Immunology
- Published
- 2020-01-22
- Volume
- 17
- Issue
- 2
- Pages
- 113-122
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC7000672
- OpenAlex
- W3001523894
- Cited by
- 111
- References
- 11
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 28 · 2023: 21 · 2022: 16 · 2021: 15 · 2020: 7 · 2019: 1
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Celgene
- Sylvia and Charles Viertel Charitable Foundation
- Wellcome Trust (109965/Z/15/Z)
- National Institute for Health and Care Research (NF-SI-0515-10005)
- National Health and Medical Research Council (1160963)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tissue-resident memory T cells, local immunity, infection immunity, tumor immunology, autoimmune skin disease, psoriasis, alopecia areata, vitiligo, pro-inflammatory response, immunotherapy, T cell biology
- MeSH terms
- Animals, Autoimmune Diseases, Communicable Diseases, Disease Models, Animal, Graft Rejection, Humans, Immunologic Memory, Neoplasms, CD4-Positive T-Lymphocytes, Autoimmunity, CD8-Positive T-Lymphocytes, Mice
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