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, and the activation marker CD69.
“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]
The section ‘Tissue-specific regulation of CTL responses’ (page not available) says that intestinal intraepithelial lymphocytes express CD69 and CD103. It does not distinguish induced from natural IELs, so it does not establish CD69 expression in both subsets separately. The E-cadherin interaction is attached to different citations in the citing sentence. (LLM, conf=0.82)
Experimental — accuracy not yet measuredUnder 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.
“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]
In “Autoimmune responses” (page not supplied), the review says IL-15 promotes NKG2D and CD94–NKG2C expression on intestinal intraepithelial lymphocytes in coeliac disease and identifies their epithelial ligands. It also associates high inhibitory CD94–NKG2A expression with an absence of villous atrophy, but does not say that the lymphocytes lose this receptor under stress or inflammation. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIL-15 is a pleiotropic cytokine produced by many different cell types that regulates development, survival, and function of peripheral lymphocytes.
“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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- 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
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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