The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3

Bennett, Craig L.; Christie, Jacinda R.; Ramsdell, Fred; Brunkow, Mary E.; Ferguson, Polly J.; Whitesell, Luke; Kelly, Thaddeus E.; Saulsbury, Frank T.; Chance, Phillip F.; Ochs, Hans D.

doi:10.1038/83713

Cited by 2,966 publications

(2,080 citation statements)

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“…These studies strongly indicate that a threshold of Treg function is required throughout life to restrain autoreactive T cells and/or inflammatory responses, and this prevents autoimmune disease onset. The early development of autoimmune disease in IPEX patients, who lack FOXP3 and Treg,23 confirms that Treg are also essential in humans 24. Functional defects in Treg in type 1 diabetes and inflammatory bowel disease have been reported,25, 26 but there are conflicting reports in the literature about reduced Treg numbers in autoimmune cohorts.…”

Section: Treg and Diseasementioning

confidence: 89%

“…Since its identification as the key transcription factor for the formation and function of Treg in mouse and humans,23, 31, 32 FOXP3 has been the subject of much investigation. Molecular mechanisms for the action of FOXP3 in shaping regulatory T cells and their critical role in maintaining lifelong tolerance are now being better understood.…”

Section: Transcriptional Control Of Treg Formation and Functionmentioning

confidence: 99%

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Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

et al. 2018

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Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T‐cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA‐based regulation of gene expression. There are well‐documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself. This type of feedforward/feedback regulatory loop is normally stable in the steady state, but can alter in response to local cues or genetic risk. This may go some way to explaining T‐cell plasticity. In addition, in chronic inflammation or autoimmunity, altered Treg/Tconv function may be influenced by changes in enhancer–promoter interactions, which are highly cell type‐specific. These interactions are impacted by genetic risk based on genome‐wide association studies and may cause subtle alterations to the gene regulatory networks controlled by or controlling FOXP3 and its target genes. Recent insights into the 3D organisation of chromatin and the mapping of noncoding regulatory regions to the genes they control are shedding new light on the direct impact of genetic risk on T‐cell function and susceptibility to inflammatory and autoimmune conditions.

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Section: Treg and Diseasementioning

confidence: 89%

Section: Transcriptional Control Of Treg Formation and Functionmentioning

confidence: 99%

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

et al. 2018

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“…Several studies have indicated that genetic defects in FOXP3 may lead to its altered levels and functionality and, indeed, autoimmune disorders have been related to various deleterious mutations in FOXP3 [34][35][36][37][38]. With respect to vitiligo, polymorphisms of FOXP3 have been associated with predispostion to the development of the disease (Table 2) [39-41].…”

Section: Forkhead Box P3mentioning

confidence: 99%

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

Dwivedi

Kemp

Laddha

et al. 2015

Autoimmunity Reviews

111

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Vitiligo is a hypomelanotic autoimmune skin disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses against melanocytes.Regulatory T cells (Tregs) are crucial to the development of self-tolerance and so are major foci in the study of autoimmune pathogenesis of vitiligo. This review will summarise recent findings concerning the role of Tregs in the pathogenesis of vitiligo. In addition, as antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, new strategies that expand or induce de novo generation of Tregs and which are currently being investigated as therapies for other autoimmune diseases, will be discussed. These approaches will highlight the opportunities for Treg cell-based therapeutics in vitiligo.4

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“…Indeed, infection of naive T cells with a retroviral vector expressing FoxP3 was sufficient to induce a regulatory phenotype in these cells 3 . Moreover, deletion or loss of function of the FoxP3 encoding gene determines an autoimmune phenotype both in humans (the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) 4 and mice (Scurfy) 5 . Functionally Tregs have been studied both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%