IPEX as a Consequence of Alternatively Spliced FOXP3

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, an...

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Bibliographic Details
Published in:Frontiers in pediatrics 2020-10, Vol.8, p.594375-594375
Main Author: Mailer, Reiner K.
Format: Article
Language:English
Subjects:
alternative splicing
CD4+ T cell
Foxp3
IPEX
isoform
Pediatrics
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Summary: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 (FOXP3Δ2), exon 7 (FOXP3Δ7), or both (FOXP3Δ2Δ7) 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.
ISSN:2296-2360
2296-2360
DOI:10.3389/fped.2020.594375