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IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction
Open accessAbstract
In this Opinion article, we discuss the function of tissues as a crucial checkpoint for the regulation of effector T cell responses, and the notion that interleukin-15 (IL-15) functions as a danger molecule that communicates to the immune system that the tissue is under attack and poises it to mediate tissue destruction. More specifically, we propose that expression of IL-15 in tissues promotes T helper 1 cell-mediated immunity and provides co-stimulatory signals to effector cytotoxic T cells to exert their effector functions and drive tissue destruction. Therefore, we think that IL-15 contributes to tissue protection by promoting the elimination of infected cells but that when its expression is chronically dysregulated, it can promote the development of complex T cell-mediated disorders associated with tissue destruction, such as coeliac disease and type 1 diabetes.
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“Both subsets of iIELs (induced and natural) express the integrin CD103, which interacts with E-cadherin on epithelial cells [299-301], and the activation marker CD69 [302, 303].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [302]
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“Under stress or inflammatory conditions, such as in celiac disease, iIELs upregulate the expression of activating NKG2D and CD94/NKG2C receptors, (which recognize MICA/B and HLA-E, respectively) while losing the expression of the inhibitory receptors CD94/NKG2A [302, 306-308].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [302]
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“Il-15 is a pleiotropic cytokine produced by many different cell types that regulates development, survival, and function of peripheral lymphocytes.30”
From CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease (2018) · cites this paper as [30]
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Metadata
- Authors
- Jabri, B., & Abadie, V.
- Affiliations
- CHU Sainte-Justine Research Center (CA)
- Corresponding author
- Abadie, Valérie
- Venue
- Nature Reviews Immunology
- Published
- 2015-11-16
- Volume
- 15
- Issue
- 12
- Pages
- 771-783
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC5079184
- OpenAlex
- W2189537077
- Cited by
- 315
- References
- 163
- Citations by year
- 2026: 11 · 2025: 34 · 2024: 44 · 2023: 20 · 2022: 32 · 2021: 48 · 2020: 29 · 2019: 30 · 2018: 25 · 2017: 31 · 2016: 11
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Chicago
- Hospital for Sick Children
- National Institute of Diabetes and Digestive and Kidney Diseases (R01_DK67180, R01DK098435, R01DK067180, DK42086, P30DK042086)
- 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 › Immune Response and Inflammation
- Keywords
- IL-15, damage-associated molecular patterns, tissue-resident T cells, tissue destruction, sterile inflammation, T cell-mediated autoimmunity, Th1 cells, cytotoxic T lymphocytes, costimulation, tissue protection, celiac disease, type 1 diabetes
- MeSH terms
- Bacterial Infections, Celiac Disease, Diabetes Mellitus, Type 1, Humans, Immunity, Cellular, Killer Cells, Natural, Protein Binding, T-Lymphocytes, Signal Transduction, CD8-Positive T-Lymphocytes, Th1 Cells, Models, Immunological, Interleukin-15, Interleukin-15 Receptor alpha Subunit
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