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Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia
Open accessAbstract
Regulatory T cells are believed to control the development and progression of autoimmunity by suppressing autoreactive T cells. Decreased numbers of CD4(+)CD25(+) FOXP3(+) T cells (Tregs) are associated with impaired immune homeostasis and development of autoimmune diseases. The transcription factors FOXP3 and NFAT1 have key roles in regulatory T-cell development and function. We show that Tregs are decreased at presentation in almost all patients with aplastic anemia; FOXP3 protein and mRNA levels also are significantly lower in patients with aplastic anemia and NFAT1 protein levels are decreased or absent. Transfection of FOXP3-deficient CD4(+)CD25(+) T cells from patients with a plasmid encoding wild-type NFAT1 resulted in increased FOXP3 expression in these cells. By NFAT1 knockdown in CD4(+)CD25(+) T cells, FOXP3 expression was decreased when NFAT1 expression was decreased. Our findings indicate that decreased NFAT1 could explain low FOXP3 expression and diminished Treg frequency in aplastic anemia. Treg defects are now implicated in autoimmune marrow failure.
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“Another major effector of damage is a type 1 T-helper (Th1) cell-skewed response of the adaptive immune system, which was also identified as the major source of IFN-g, accompanied by a reduction in regulatory T cells (Tregs) in the marrow.60”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [60]
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Metadata
- Authors
- Solomou, E. E., Rezvani, K., Mielke, S., Malide, D., Keyvanfar, K., Visconte, V., Kajigaya, S., Barrett, A. J., & Young, N. S.
- Affiliations
- Hematology Branch and
- National Institutes of Health (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-09-01
- Volume
- 110
- Issue
- 5
- Pages
- 1603-1606
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1975843
- OpenAlex
- W2066935327
- Cited by
- 225
- References
- 24
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 10 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 21 · 2019: 10 · 2018: 18 · 2017: 19 · 2016: 9 · 2015: 11 · 2014: 11 · 2013: 10 · 2012: 11
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- regulatory T cells, CD4+CD25+ T cells, Foxp3, NFAT1, acquired aplastic anemia, Treg deficiency, immune homeostasis, transcription factors, Treg reprogramming
- MeSH terms
- Adolescent, Adult, Anemia, Aplastic, Autoimmune Diseases, Cells, Cultured, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Transfection, Autoimmunity, T-Lymphocytes, Regulatory, NFATC Transcription Factors, Forkhead Transcription Factors
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