Transcription factors (TFs) are key cellular proteins that control biological processes and enable cells to maintain their function and respond to internal and external stimuli. By recognizing and binding to specific regulatory DNA motifs, TFs modify the expression of target genes. Variations in the activity and specificity of TFs are believed to play an important role in evolutionary adaptation. Deleterious alterations in the transcriptional regulatory system may, however, also be associated with disease. Since immunological pathways and immune cell responses are also controlled by TFs, it is not surprising to see that defects in numerous TFs have been associated with inborn errors of immunity (IEI). Pathogenic mutations in TFs have been associated with nearly all categories of IEI, from combined cellular and humoral immunodeficiencies, over predominantly antibody deficiencies and immune dysregulation disorders, to congenital defects in innate immunity and phagocytes. This emphasizes the widespread role of TFs across immune responses.
The dynamic behavior of TFs in binding DNA motifs, protein complex formation, and ultimately gene expression is a challenging subject. Depending on the site and type of mutations, different defects in the same TF can give rise to quite diverse clinical pictures. Furthermore, certain genetic alterations in IEI-related genes may cause predisposition to the development of autoimmune disease (e.g. AIRE, FOXP3, IKZF1, NFKB1/NFKB2, STATs, etc) and/or malignancy (e.g. GATA2, NFKB1, IKZF1, etc).
Advances in Next-Generation Sequencing (NGS) and animal models of human disease have contributed to identifying pathogenic variants and understanding mechanisms that are critical for host immunity. In this research topic, we review molecular mechanisms and clinical/immunological phenotypes identified from TF mutations in the field of IEI. Several defects of transcription factors associated with abnormal expression or function were reported in those IEI. To understand the complexity of the genetic and clinical features of transcription factor-associated IEI, we focus on the underlying molecular mechanisms and clinical/immunological phenotypes, in addition to diagnosis and treatment options.
In this Research Topic, we aim to bring together researchers and clinicians to focus on the role of TFs in IEI. More specifically, we aim to outline our current understanding of the molecular mechanisms by which defects in TFs lead to immune dysfunction and how they are likely to be a major source of phenotypic variability. Also, we discuss genetic diagnosis and functional validation as well as clinical and immunologic tests as early diagnosis and management of the disease are beneficial to the patients.
We welcome the submission of Original Research, Review, Mini Review, Case Report, Clinical Trial, Opinion, and Perspective articles. We welcome submissions covering, but not limited to, the following sub-topics:
• Role of TFs in IEI: an overview of different defects in TFs associated with IEI
• TFs at the crossroad between autoimmune disease and IEI
• TFs at the crossroad between cancer predisposition and IEI
• Overview of laboratory techniques/tools to validate defects in TFs
• The different faces of STAT family mutations in IEI
• ZNF341 variants and hyper- IgE syndrome
• GATA2 -associated diseases and their impact on immunity
• The different faces of IKZF family mutations in IEI
• NFKB family allelic variants and phenotypes in IEI
• AIRE associated diseases in IEI
• Mutations in FOXP3 and their impact on immunity
• Inborn errors of IRF family and susceptibility to infections (e.g., Sars CoV2, Influenza virus)
• Transcription factors and their role in host immune responses: what have we learned from mouse models
• Alterations in TFs and common variable immune deficiency
• Treatment modalities for IEI caused by gain-of-function mutations in TFs.
Transcription factors (TFs) are key cellular proteins that control biological processes and enable cells to maintain their function and respond to internal and external stimuli. By recognizing and binding to specific regulatory DNA motifs, TFs modify the expression of target genes. Variations in the activity and specificity of TFs are believed to play an important role in evolutionary adaptation. Deleterious alterations in the transcriptional regulatory system may, however, also be associated with disease. Since immunological pathways and immune cell responses are also controlled by TFs, it is not surprising to see that defects in numerous TFs have been associated with inborn errors of immunity (IEI). Pathogenic mutations in TFs have been associated with nearly all categories of IEI, from combined cellular and humoral immunodeficiencies, over predominantly antibody deficiencies and immune dysregulation disorders, to congenital defects in innate immunity and phagocytes. This emphasizes the widespread role of TFs across immune responses.
The dynamic behavior of TFs in binding DNA motifs, protein complex formation, and ultimately gene expression is a challenging subject. Depending on the site and type of mutations, different defects in the same TF can give rise to quite diverse clinical pictures. Furthermore, certain genetic alterations in IEI-related genes may cause predisposition to the development of autoimmune disease (e.g. AIRE, FOXP3, IKZF1, NFKB1/NFKB2, STATs, etc) and/or malignancy (e.g. GATA2, NFKB1, IKZF1, etc).
Advances in Next-Generation Sequencing (NGS) and animal models of human disease have contributed to identifying pathogenic variants and understanding mechanisms that are critical for host immunity. In this research topic, we review molecular mechanisms and clinical/immunological phenotypes identified from TF mutations in the field of IEI. Several defects of transcription factors associated with abnormal expression or function were reported in those IEI. To understand the complexity of the genetic and clinical features of transcription factor-associated IEI, we focus on the underlying molecular mechanisms and clinical/immunological phenotypes, in addition to diagnosis and treatment options.
In this Research Topic, we aim to bring together researchers and clinicians to focus on the role of TFs in IEI. More specifically, we aim to outline our current understanding of the molecular mechanisms by which defects in TFs lead to immune dysfunction and how they are likely to be a major source of phenotypic variability. Also, we discuss genetic diagnosis and functional validation as well as clinical and immunologic tests as early diagnosis and management of the disease are beneficial to the patients.
We welcome the submission of Original Research, Review, Mini Review, Case Report, Clinical Trial, Opinion, and Perspective articles. We welcome submissions covering, but not limited to, the following sub-topics:
• Role of TFs in IEI: an overview of different defects in TFs associated with IEI
• TFs at the crossroad between autoimmune disease and IEI
• TFs at the crossroad between cancer predisposition and IEI
• Overview of laboratory techniques/tools to validate defects in TFs
• The different faces of STAT family mutations in IEI
• ZNF341 variants and hyper- IgE syndrome
• GATA2 -associated diseases and their impact on immunity
• The different faces of IKZF family mutations in IEI
• NFKB family allelic variants and phenotypes in IEI
• AIRE associated diseases in IEI
• Mutations in FOXP3 and their impact on immunity
• Inborn errors of IRF family and susceptibility to infections (e.g., Sars CoV2, Influenza virus)
• Transcription factors and their role in host immune responses: what have we learned from mouse models
• Alterations in TFs and common variable immune deficiency
• Treatment modalities for IEI caused by gain-of-function mutations in TFs.
