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IPEX as a Consequence of Alternatively Spliced FOXP3.

ABSTRACT: 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 (FOXP3?2), exon 7 (FOXP3?7), or both (FOXP3?2?7) 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.

SUBMITTER: Mailer RK

PROVIDER: S-EPMC7609600 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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IPEX as a Consequence of Alternatively Spliced FOXP3.

Mailer Reiner K RK

Frontiers in pediatrics 20201021

The transcription factor FOXP3 controls the immunosuppressive program in CD4<sup>+</sup> T cells that is crucial for systemic immune regulation. Mutations of the single X-chromosomal <i>FOXP3</i> 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 t ...[more]

PMID: 33194927

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