Regulatory T Cells and Profile of FOXP3 Isoforms Expression in Peripheral Blood of Patients with Myelodysplastic Syndromes

Дудина, Г. А.; Донецкова, А Д; Литвина, М М; Mitin, A.N.; Митина, Т. А.; Polyakov, S.A.

doi:10.1155/2018/8487403

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) (39), Hashimoto's thyroiditis (HT) (43), giant cell arteritis (GCA) (44), relapsing-remitting multiple sclerosis (RRMS) (45) and coeliac disease (CD) (46) showed upregulated FOXP3DE2 isoforms in peripheral blood mononuclear cells (PBMCs) compared to control subjects. On the other hand, patients with rheumatoid arthritis (RA) (47), systemic lupus erythematosus (SLE) (47,48), inflammatory bowel diseases (IBD) (29), myelodysplastic syndromes (MDS) (49) and RRMS (50) showed lower or normal FOXP3DE2 isoform levels. The inconsistent results shown in the studies investigating the same disease might be partly due to the differences in the disease stages and the detection methods.…”

Section: Changes Of Foxp3fl and Foxp3de2 Isoforms In Autoimmune And I...mentioning

confidence: 99%

Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease

Luo,

Zhang,

Saleh

et al. 2023

Front. Immunol.

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Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs. The balance of FOXP3 splicing isoforms is related to autoimmune diseases, inflammatory diseases, and cancers. In response to environmental challenges, FOXP3 transcription and splicing can be finely regulated by T cell antigen receptor stimulation, glycolysis, fatty acid oxidation, and reactive oxygen species, with various signaling pathways involved. Strategies targeting energy metabolism and FOXP3 splicing isoforms in Tregs may provide potential new approaches for the treatment of autoimmune diseases, inflammatory diseases, and cancers. In this review, we summarize recent discoveries about the FOXP3 splicing isoforms and address the metabolic regulation and specific functions of FOXP3 splicing isoforms in Tregs.

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Section: Changes Of Foxp3fl and Foxp3de2 Isoforms In Autoimmune And I...mentioning

confidence: 99%

Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease

Luo,

Zhang,

Saleh

et al. 2023

Front. Immunol.

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IPEX as a Consequence of Alternatively Spliced FOXP3

Mailer

2020

Front. Pediatr.

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The transcription factor FOXP3 controls the immunosuppressive program in CD4 + T cells that is crucial for systemic immune regulation. Mutations of the single X-chromosomal FOXP3 gene in male individuals cause the inherited autoimmune disease immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome. Insufficient gene expression and impaired function of mutant FOXP3 protein prevent the generation of anti-inflammatory regulatory T (Treg) cells and fail to inhibit autoreactive T cell responses. Diversification of FOXP3 functional properties is achieved through alternative splicing that leads to isoforms lacking exon 2 (FOXP3 2), exon 7 (FOXP3 7), or both (FOXP3 2 7) specifically in human CD4 + T cells. Several IPEX mutations targeting these exons or promoting their alternative splicing revealed that those truncated isoforms cannot compensate for the loss of the full-length isoform (FOXP3fl). In this review, IPEX mutations that change the FOXP3 isoform profile and the resulting consequences for the CD4 + T-cell phenotype are discussed.

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A Killer Disarmed: Natural Killer Cell Impairment in Myelodysplastic Syndrome

Arellano-Ballestero

Sabry

Lowdell

2023

Cells

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Myelodysplastic syndrome (MDS) treatment remains a big challenge due to the heterogeneous nature of the disease and its ability to progress to acute myeloid leukemia (AML). The only curative option is allogeneic hematopoietic stem cell transplantation (HSCT), but most patients are unfit for this procedure and are left with only palliative treatment options, causing a big unmet need in the context of this disease. Natural killer (NK) cells are attractive candidates for MDS immunotherapy due to their ability to target myeloid leukemic cells without prior sensitization, and in recent years we have seen an arising number of clinical trials in AML and, recently, MDS. NK cells are reported to be highly dysfunctional in MDS patients, which can be overcome by adoptive NK cell immunotherapy or activation of endogenous NK cells. Here, we review the role of NK cells in MDS, the contribution of the tumor microenvironment (TME) to NK cell impairment, and the most recent data from NK cell-based clinical trials in MDS.

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Regulatory T Cells and Profile of FOXP3 Isoforms Expression in Peripheral Blood of Patients with Myelodysplastic Syndromes

Cited by 3 publications

References 23 publications

Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease

Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease

IPEX as a Consequence of Alternatively Spliced FOXP3

A Killer Disarmed: Natural Killer Cell Impairment in Myelodysplastic Syndrome

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