Cutting edge: protein phosphatase 2A confers susceptibility to autoimmune disease through an IL-17-dependent mechanism
Open accessAbstract
The contribution of individual molecular aberrations to the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease that affects multiple organs, is often difficult to evaluate because of the presence of abundant confounding factors. To assess the effect of increased expression of the phosphatase protein phosphatase 2A (PP2A) in T cells, as recorded in SLE patients, we generated a transgenic mouse that overexpresses the PP2Ac subunit in T cells. The transgenic mouse displays a heightened susceptibility to immune-mediated glomerulonephritis in the absence of other immune defects. CD4(+) T cells produce increased amounts of IL-17 while the number of neutrophils in the peripheral blood is increased. IL-17 neutralization abrogated the development of glomerulonephritis. We conclude that increased PP2Ac expression participates in SLE pathogenesis by promoting inflammation through unchecked IL-17 production and facilitating the development of end-organ damage.
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Neutralization of IL-17 rescued the glomerulonephritis development.
“neutralization of IL-17 rescued the glomerulonephritis development [85].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [85]
CD4+ T-cells showed a deviated cytokine production profile, with increased levels of IL-17 (Il17a and Il17b).
“CD4 + T-cells showed a deviated cytokine production profile, with increased levels of IL-17 (Il17a and Il17b).”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [85]
An increased number of neutrophils in the blood sustained the increased inflammation characterizing this model.
“An increased number of neutrophils in the blood sustained the increased inflammation characterizing this model.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [85]
Transgenic mice with wild-type Cα overexpression specifically in T-cells achieved a 30% increase in Cα mRNA and protein expression.
“A 30% increase in Cα mRNA and protein expression was achieved.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [85]
These mice showed increased susceptibility to immune-mediated glomerulonephritis, in the absence of other immune defects.
“These mice showed increased susceptibility to immune-mediated glomerulonephritis, in the absence of other immune defects.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [85]
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Physiologic functions of PP2A: Lessons from genetically modified mice
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Targeting PP2A in cancer: an underrated option
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- Authors
- Crispín, J. C., Apostolidis, S. A., Rosetti, F., Keszei, M., Wang, N., Terhorst, C., Mayadas, T. N., & Tsokos, G. C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- Department of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215
- Corresponding author
- Tsokos, George C
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04
- Volume
- 188
- Issue
- 8
- Pages
- 3567-3571
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3324672
- OpenAlex
- W2164882082
- Cited by
- 64
- References
- 23
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 1
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (R01-A-1068787)
- National Heart, Lung, and Blood Institute (R01HL065095)
- National Institute of Allergy and Infectious Diseases (R01AI068787)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- protein phosphatase 2A, PP2A catalytic subunit, systemic lupus erythematosus, IL-17, CD4+ T cells, glomerulonephritis, neutrophils, transgenic mice, autoimmune disease susceptibility, target organ damage, inflammation
- MeSH terms
- Animals, Disease Models, Animal, Disease Susceptibility, Glomerulonephritis, Humans, Lupus Erythematosus, Systemic, Mice, Inbred C57BL, Mice, Transgenic, CD4-Positive T-Lymphocytes, Gene Expression, Interleukin-17, Protein Subunits, Mice, Protein Phosphatase 2, Antibodies, Neutralizing
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