IPEX as a Consequence of Alternatively Spliced FOXP3
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IPEX as a Consequence of Alternatively Spliced FOXP3. / Mailer, Reiner K.
In: FRONT PEDIATR, Vol. 8, 2020, p. 594375.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - IPEX as a Consequence of Alternatively Spliced FOXP3
AU - Mailer, Reiner K
N1 - Copyright © 2020 Mailer.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.3389/fped.2020.594375
DO - 10.3389/fped.2020.594375
M3 - SCORING: Review article
C2 - 33194927
VL - 8
SP - 594375
JO - FRONT PEDIATR
JF - FRONT PEDIATR
SN - 2296-2360
ER -