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, and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2020.594375/full |
| _version_ | 1818209255250984960 |
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| author | Reiner K. Mailer |
| author_facet | Reiner K. Mailer |
| author_sort | Reiner K. Mailer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T04:57:48Z |
| format | Article |
| id | doaj.art-99f0d9f89dd743288517d07f2fc9573e |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-12T04:57:48Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-99f0d9f89dd743288517d07f2fc9573e2022-12-22T00:37:19ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602020-10-01810.3389/fped.2020.594375594375IPEX as a Consequence of Alternatively Spliced FOXP3Reiner K. MailerThe 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.https://www.frontiersin.org/articles/10.3389/fped.2020.594375/fullFoxp3isoformalternative splicingIPEXCD4+ T cell |
| spellingShingle | Reiner K. Mailer IPEX as a Consequence of Alternatively Spliced FOXP3 Frontiers in Pediatrics Foxp3 isoform alternative splicing IPEX CD4+ T cell |
| title | IPEX as a Consequence of Alternatively Spliced FOXP3 |
| title_full | IPEX as a Consequence of Alternatively Spliced FOXP3 |
| title_fullStr | IPEX as a Consequence of Alternatively Spliced FOXP3 |
| title_full_unstemmed | IPEX as a Consequence of Alternatively Spliced FOXP3 |
| title_short | IPEX as a Consequence of Alternatively Spliced FOXP3 |
| title_sort | ipex as a consequence of alternatively spliced foxp3 |
| topic | Foxp3 isoform alternative splicing IPEX CD4+ T cell |
| url | https://www.frontiersin.org/articles/10.3389/fped.2020.594375/full |
| work_keys_str_mv | AT reinerkmailer ipexasaconsequenceofalternativelysplicedfoxp3 |