Distinct p21 requirements for regulating normal and self-reactive T cells through IFN-γ production
Open accessAbstract
Self/non-self discrimination characterizes immunity and allows responses against pathogens but not self-antigens. Understanding the principles that govern this process is essential for designing autoimmunity treatments. p21 is thought to attenuate autoreactivity by limiting T cell expansion. Here, we provide direct evidence for a p21 role in controlling autoimmune T cell autoreactivity without affecting normal T cell responses. We studied C57BL/6, C57BL/6/lpr and MRL/lpr mice overexpressing p21 in T cells and showed reduced autoreactivity and lymphadenopathy in C57BL/6/lpr and reduced mortality in MRL/lpr mice. p21 inhibited effector/memory CD4+ CD8+ and CD4−CD8−lpr T cell accumulation without altering defective lpr apoptosis. This was mediated by a previously non-described p21 function in limiting T cell overactivation and overproduction of IFN-γ, a key lupus cytokine. p21 did not affect normal T cell responses, revealing differential p21 requirements for autoreactive and normal T cell activity regulation. The underlying concept of these findings suggests potential treatments for lupus and autoimmune lymphoproliferative syndrome, without compromising normal immunity.
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p21 may have roles outside of cell cycle inhibition and its upregulation is not specific to senescence.
“For example, p21 may have roles outside of cell cycle inhibition [156] and its upregulation is not specific to senescence [157].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [156]
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BackgroundRackov, G., Zaniani, P. T., Colomo, S., Shokri, R., Álvarez‐Mon, M., Martínez‐A, C., & Balomenos, D. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.19.427239
“for the in vivo IFN-γ and lupus-like symptoms of lpr mice (13).”
BackgroundInfluentialSelf-citationWu, Y., Shi, B., He, Y., Wang, S., Zhou, J., Qi, J., Ding, J., & Wang, Z. (2024) · The FASEB Journal · doi:10.1096/fj.202401909r
- Authors
- Daszkiewicz, L., Vázquez-Mateo, C., Rackov, G., Ballesteros-Tato, A., Weber, K., Madrigal-Avilés, A., Di Pilato, M., Fotedar, A., Fotedar, R., Flores, J. M., Esteban, M., Martínez-A, C., & Balomenos, D.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Sidney Kimmel Cancer Center (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Balomenos, Dimitrios
- Venue
- Scientific Reports
- Published
- 2015-01-09
- Volume
- 5
- Issue
- 1
- Pages
- 7691-7691
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4287747
- OpenAlex
- W2047394198
- Cited by
- 26
- References
- 56
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- “la Caixa” Foundation
- Comunidad de Madrid
- Ministerio de Economía y Competitividad
- Ministerio de Ciencia e Innovación
- Consejería de Sanidad, Comunidad de Madrid
- National Institute on Minority Health and Health Disparities (L60 MD002502)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- p21, interferon-gamma, T cell autoreactivity, systemic lupus erythematosus, autoimmune lymphoproliferative syndrome, lpr mice, MRL/lpr mice, CD4+CD8+ T cells, lymphadenopathy, autoimmunity, self/non-self discrimination
- MeSH terms
- Animals, Autoimmune Diseases, Cells, Cultured, Immunologic Memory, Interferon-gamma, Lymphocyte Activation, Mice, Inbred C57BL, Ovalbumin, T-Lymphocytes, Vaccinia virus, CD4-Positive T-Lymphocytes, Apoptosis, CD8-Positive T-Lymphocytes, Mice, Inbred MRL lpr, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Mice
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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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