Genetic and epigenetic studies of FOXP3 in asthma and allergy

Abstract

Multiple factors interact to trigger allergic diseases, including individual genetic background and factors related to the environment such as exposure to allergens, air pollution and respiratory infections. The FOXP3 transcription factor is constitutively expressed in CD4+CD25+FOXP3+ regulatory T cells (Tregs) and is critical for the maintenance of immune homeostasis. For example, FOXP3 is responsible for the suppression of the Th2 response following exposure to allergens. Studies have shown that expression of the FOXP3 gene is reduced in patients with asthma and allergies compared to healthy controls. Therefore, the impairment of FOXP3 function caused by genetic polymorphisms and/or epigenetic mechanisms may be involved in the etiology of asthma and other allergic diseases. This review discusses some aspects of the role of FOXP3 in the development of asthma and allergy, with a particular emphasis on genetic and epigenetic factors.

The Impact of FOXP3 Polymorphism on the Risk of Allergic Rhinitis: A Meta‐Analysis

“…Additional meta‐analyses of other SNPs or haplotype are required to give more comprehensive insight into the role of FOXP3 polymorphisms in the susceptibility to allergic rhinitis. Considering the close functional link between asthma/allergy and FOXP3 protein or CD4 + CD25 + FOXP3 + regulatory T cells (Tregs) (Marques et al., ), it is possible that certain or unidentified variations of the FOXP3 gene are involved in an increased allergic rhinitis risk by modulating the biological properties of FOXP3 protein.…”

“…Natural CD4 + CD25 + T‐regulatory cells primarily expressed FOXP3 protein, which is capable of influencing the immune responses through modulating the proliferation, cytokine production and suppressive activity of T cells (Hori et al., ; Williams & Rudensky, ; Paik et al., ; Park et al., ; Pesenacker et al., ). The functional impairment of FOXP3 protein may be implicated in the pathogenesis of several human clinical disorders or syndromes, such as immune dysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome (IPEX), X‐linked autoimmunity allergic dysregulation (XLAAD) and malignancies (L. Zhang et al., ; Bottema et al., ; Benayoun et al., ; Guo et al., ; Y. Zhang et al., ; Marques et al., ).…”

Association of FOXP3 Single Nucleotide Polymorphisms With Clinical Outcomes After Allogenic Hematopoietic Stem Cell Transplantation

“…Many studies have shown that the regulatory mechanism of gene expression is controlled by genomic polymorphisms. Single nucleotide polymorphisms (SNPs) in FOXP3 have been associated with various diseases [ 11 ], including asthma [ 12 ], preeclampsia [ 13 ], systemic lupus erythematosus [ 14 ], autoimmune thyroid disease [ 15 ], lung cancer [ 16 ], breast cancer [ 17 ], and colorectal cancer [ 18 ]. Recently, several studies reported that FOXP3 SNPs are associated with allograft outcomes after renal transplantation, but there is ongoing debate over whether FOXP3 SNPs have a positive or negative association with allograft outcomes [ 19 20 21 22 ].…”

The FOXP3 rs3761547 Gene Polymorphism in Multiple Sclerosis as a Male-Specific Risk Factor

“…This polymorphisms may presumably change gene expression by modifying the binding specificity of transcription factors to their binding sites and by altering the kinetics of transcription initiation (Hanel et al 2011 ). Moreover, SNPs in FOXP3 gene can influence miRNA, gene splicing or encoded protein structure and activity (Marques et al 2015 ). We analyzed three of the known five polymorphisms the promoter region of FOXP3: − 2383C/T (rs3761549), − 3279G/T (rs3761548), and − 3499T/C (rs3761547).…”