Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

被引:98
作者
Colamatteo, Alessandra [1 ]
Carbone, Fortunata [2 ,3 ]
Bruzzaniti, Sara [2 ,4 ]
Galgani, Mario [1 ,2 ]
Fusco, Clorinda [1 ]
Maniscalco, Giorgia Teresa [5 ]
Di Rella, Francesca [6 ]
de Candia, Paola [7 ]
De Rosa, Veronica [2 ,3 ]
机构
[1] Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Treg Cell Lab, Naples, Italy
[2] CNR, IEOS, Lab Immunol, Naples, Italy
[3] Fdn Santa Lucia, Unita NeuroImmunol, Rome, Italy
[4] Univ Napoli Federico II, Dipartimento Biol, Naples, Italy
[5] Azienda Osped A Cardarelli, Ctr Reg Sclerosi Multipla, Dipartimento Neurol, Naples, Italy
[6] Fdn G Pascale, IRCCS, Ist Nazl Tumori, Clin & Expt Senol, Naples, Italy
[7] IRCCS MultiMed, Milan, Italy
关键词
Foxp3; Treg cells; epigenetic regulation; stability; autoimmunity; T-CELL FUNCTION; TRANSCRIPTION FACTOR FOXP3; BOX P3 FOXP3; TGF-BETA; IMMUNE DYSREGULATION; CUTTING EDGE; SUPPRESSIVE ACTIVITY; MULTIPLE-SCLEROSIS; SELF-TOLERANCE; TARGET GENES;
D O I
10.3389/fimmu.2019.03136
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4(+) T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors.
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页数:20
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