Cardiovascular System ; Forkhead Transcription Factors ; Humans

Chronic Disease ; Forkhead Transcription Factors ; Hepatitis, Viral, Human ; Humans

It is now established that CD4(+)CD25(+)regulatory T (Treg) cells expressing transcription factor FOXP3, a regulatory subpopulation of T cells, is indispensable for the maintenance of immunological self-tolerance and immune homeostasis. FOXP3 expression in Treg cells is specific and it is the key control factor for the development, activation and function of Treg cells. At present, CD4(+)FOXP3(+)T lymphocytes are often used to define Treg cells for scientific research. But recent studies show that human CD4(+)FOXP3(+)T cells are phenotypically and functionally heterogeneous, including suppressive and non suppressive T cells. The different functions of these cell subsets can be distinguished by phenotypic differences. This review discusses the recent research progress about phenotypic characteristics and functional heterogeneity of CD4(+)FOXP3(+)T cell subsets.
Forkhead Transcription Factors ; immunology ; Humans ; T-Lymphocytes, Regulatory ; immunology

Regulatory T (Treg) cells are a special immunosuppressive subset of cluster of differentiation 4-positive (CD4^+‍)‍-T lymphocytes and play a pivotal role in the establishment of immune homeostasis in vivo (Zhang et al., 2021). The transcription factor forkhead box protein P3 (Foxp3) is the master marker of Treg cells, which is highly expressed in Treg cells and is also essential for their suppressive function (Hori et al., 2003). In addition to Foxp3, other regulators of Treg cells have been discovered (Wu et al., 2017, 2022; Wu and Sun, 2023a, 2023b); however, a deeper understanding of the regulation of these cells is required.
T-Lymphocytes, Regulatory ; Gene Expression Regulation ; Forkhead Transcription Factors/metabolism*

Forkhead Transcription Factors ; genetics ; Gene Expression Regulation ; Humans ; Procollagen ; genetics ; Transcription, Genetic

OBJECTIVE: To analyze the clinical manifestations and gene variants of patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). METHODS: Clinical data of 7 pedigrees affected with BPES were collected, and genomic DNA was extracted from peripheral blood samples of the probands and their relatives. All exons of the FOXL2 gene were subjected to Sanger sequencing. Those with negative findings were further screened by targeted capture and next generation sequencing (NGS) and microarray analysis. Pathogenicity of candidate variants were predicted by search of PubMed and related databases, and the impact of the variants was interpreted by protein prediction software. Diagnosis was confirmed by clinical phenotype, medical history and mutation analysis. RESULTS: A pathogenic variant was identified in six of the 7 pedigrees, which included four known pathogenic variants and one novel FOXL2 c.299dupA variant. A heterozygous 3q22.3q23 deletion, which encompassed the FOXL2 gene, was identified in another pedigree.As predicted, the c.299dupA frameshift mutation of FOXL2 gene can lead to the premature termination of protein translation, which is pathogenic. CONCLUSION A novel and 5 known pathogenic variants have been identified in six pedigrees affected with BPES by the combined Sanger sequencing, target capture NGS and microarray analysis. Above findings have enabled genetic counseling and prenatal diagnosis for these pedigrees.
Blepharophimosis/genetics* ; Forkhead Box Protein L2/genetics* ; Forkhead Transcription Factors/genetics* ; Humans ; Mutation ; Pedigree ; Phenotype ; Skin Abnormalities ; Urogenital Abnormalities

OBJECTIVETo study the expression of Foxp3 and NFAT1 protein in peripheral blood (PB) in children with aplastic anemia (AA) and their roles in the pathogenesis of AA.

METHODSThe expression levels of Foxp3 and NFAT1 protein of mononuclear cells in PB were measured by Western blot in 68 children with AA before and after treatment and in 60 normal children (control group). The correlation between Foxp3 and NFAT1 protein expression and the correlation of the Foxp3 and NFAT1 protein expression with blood Hb, WBC and platelet levels were analyzed.

RESULTSThe expression levels of Foxp3 and NFAT1 protein in PB in the acute phase in the AA group were significantly lower than in the control group (P<0.05). After treatment (recovery phase) the expression levels of Foxp3 and NFAT1 protein increased obviously compared with those in the acute phase (P<0.05). The Foxp3 protein level was positively correlated with the NFAT1 protein level (r=0.812, P<0.05). Both the Foxp3 and NFAT1 protein levels were positively correlated with blood Hb, WBC and platelet levels in children with AA in the recovery phase (r=0.537, 0.579, 0.655 respectively; P<0.05).

CONCLUSIONSThe Foxp3 and NFAT1 protein levels in PB are reduced in children with AA, suggesting that they are involved in the pathogenesis of AA. The measurement of Foxp3 and NFAT1 protein levels may be useful in the severity evaluation of AA.

Adolescent ; Anemia, Aplastic ; blood ; etiology ; Child ; Child, Preschool ; Female ; Forkhead Transcription Factors ; blood ; Humans ; Male ; NFATC Transcription Factors ; blood

OBJECTIVES: To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice. METHODS: Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing. RESULTS: HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM. CONCLUSIONS T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.
Animals ; Bone Regeneration ; Diabetes Mellitus, Type 2 ; Forkhead Transcription Factors ; Male ; Mice ; Mice, Inbred C57BL ; TCF Transcription Factors ; Th17 Cells

OBJECTIVETo review the current research into Foxp3(+) regulatory T cells (Treg) cell surface molecules, plasticity of Treg cells and mechanisms of Treg cell suppression and to explore the possibilities to interfere in Treg cell suppression of anti-tumor immunity.

DATA SOURCESA literature search of all English articles was performed on the online electronic PubMed database dated 1995 to 2010. The keywords searched included: CD4(+)CD25(+)Foxp3(+) regulatory T lymphocytes, cancer, and immunotherapy. After finding relevant articles within these search limits, a manual search was conducted through the references from these articles.

STUDY SELECTIONArticles regarding the role of Treg cells in tumor immunity and the utility of Treg cells in tumor immunotherapy.

RESULTSThe results show that significant numbers of Treg cells are found in many tumors and it has been shown that the number of tumor infiltrating Treg cells correlates with adverse clinic outcomes. Treg cells are emerging as a key component of acquired tolerance to tumors.

CONCLUSIONSSeveral mechanisms of immunosuppression can be mediated by Treg cell function. Distinct immunosuppressive molecules expressed by Treg cells or diverse molecules related to Treg induction or migration represent potential drug targets for cancer immunotherapy.

Forkhead Transcription Factors ; metabolism ; Humans ; Immunosuppression ; methods ; Immunotherapy ; methods ; Neoplasms ; immunology ; therapy ; T-Lymphocytes, Regulatory ; metabolism

CD4(+)CD25(+) regulatory T cells are thought to be a subgroup of cells which have the function of immune suppression. 5 to 10 percentage of peripheral CD4(+) T cells and 1% - 2% of peripheral mononuclear cells are CD4(+)CD25(+) regulatory T cells in mouse or healthy human. They can suppress immune response through many pathways and sustain the stabilization of internal environment. Idiopathic thrombocytopenic purpura is a kind of autoimmunity disease which mainly has a manifestation of hemorrhage in some locations such as skin, mucosa or viscera. Recent findings support that CD4(+)CD25(+) regulatory T cells are relevant to the morbidity of idiopathic thrombocytopenic purpura. In this review, the recent advance on characteristics and function of CD4(+)CD25(+) regulatory T cells, pathogenesis of idiopathic thromocytopenic purpura and role CD4(+)CD25(+) regulatory T cells in pathogenesis of idiopathic thrombocytopenic purpura were summarized.
Forkhead Transcription Factors ; physiology ; Humans ; Purpura, Thrombocytopenic ; etiology ; immunology ; T-Lymphocytes, Regulatory ; immunology