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Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease

Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3...

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Autores principales: Luo, Zhidan, Zhang, Yihua, Saleh, Qais Waleed, Zhang, Jie, Zhu, Zhiming, Tepel, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588449/
https://www.ncbi.nlm.nih.gov/pubmed/37868998
http://dx.doi.org/10.3389/fimmu.2023.1278560
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author Luo, Zhidan
Zhang, Yihua
Saleh, Qais Waleed
Zhang, Jie
Zhu, Zhiming
Tepel, Martin
author_facet Luo, Zhidan
Zhang, Yihua
Saleh, Qais Waleed
Zhang, Jie
Zhu, Zhiming
Tepel, Martin
author_sort Luo, Zhidan
collection PubMed
description Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs. The balance of FOXP3 splicing isoforms is related to autoimmune diseases, inflammatory diseases, and cancers. In response to environmental challenges, FOXP3 transcription and splicing can be finely regulated by T cell antigen receptor stimulation, glycolysis, fatty acid oxidation, and reactive oxygen species, with various signaling pathways involved. Strategies targeting energy metabolism and FOXP3 splicing isoforms in Tregs may provide potential new approaches for the treatment of autoimmune diseases, inflammatory diseases, and cancers. In this review, we summarize recent discoveries about the FOXP3 splicing isoforms and address the metabolic regulation and specific functions of FOXP3 splicing isoforms in Tregs.
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spelling pubmed-105884492023-10-21 Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease Luo, Zhidan Zhang, Yihua Saleh, Qais Waleed Zhang, Jie Zhu, Zhiming Tepel, Martin Front Immunol Immunology Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs. The balance of FOXP3 splicing isoforms is related to autoimmune diseases, inflammatory diseases, and cancers. In response to environmental challenges, FOXP3 transcription and splicing can be finely regulated by T cell antigen receptor stimulation, glycolysis, fatty acid oxidation, and reactive oxygen species, with various signaling pathways involved. Strategies targeting energy metabolism and FOXP3 splicing isoforms in Tregs may provide potential new approaches for the treatment of autoimmune diseases, inflammatory diseases, and cancers. In this review, we summarize recent discoveries about the FOXP3 splicing isoforms and address the metabolic regulation and specific functions of FOXP3 splicing isoforms in Tregs. Frontiers Media S.A. 2023-10-06 /pmc/articles/PMC10588449/ /pubmed/37868998 http://dx.doi.org/10.3389/fimmu.2023.1278560 Text en Copyright © 2023 Luo, Zhang, Saleh, Zhang, Zhu and Tepel https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Luo, Zhidan
Zhang, Yihua
Saleh, Qais Waleed
Zhang, Jie
Zhu, Zhiming
Tepel, Martin
Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title_full Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title_fullStr Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title_full_unstemmed Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title_short Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
title_sort metabolic regulation of forkhead box p3 alternative splicing isoforms and their impact on health and disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588449/
https://www.ncbi.nlm.nih.gov/pubmed/37868998
http://dx.doi.org/10.3389/fimmu.2023.1278560
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