Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells
Abstract
:1. Introduction
2. Transcription Factors in a Core eTreg Transcriptional Program
2.1. IRF4
2.2. BATF and JunB
2.3. Blimp1
2.4. Myb
2.5. NF-κB
2.6. Id2, Id3, E2A, and HEB
2.7. TCF1 and LEF1
2.8. Foxo1
3. Transcription Factors Regulating Differentiation of Distinct Subsets of eTreg Cells
3.1. T-Bet, GATA3, RORγt, Bcl6 and STAT5
3.2. c-Maf
3.3. STAT3
3.4. PPARγ and RORα
4. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Name | Expression | Function | Target | Upstream Regulator | Ref. |
---|---|---|---|---|---|
IRF4 | eTreg | Regulates eTreg differentiation | ICOS, Blimp1, FGL2, ST2, GATA3, CCR8, CTLA4, KLRG1, IL-10, CCR6 | TCR+CD28+IL-2 | [16,53,54] |
BATF | eTreg | Promotes expression of eTreg-related genes | ICOS, GATA3, ST2, KLRG1, CCR4, CCR6 | TCR+CD28+IL-2 | [17,54,55] |
JunB | eTreg | Promotes expression of eTreg-related genes | ICOS, FGL2, CTLA4, TIGIT, KLRG1 | TCR+CD28+IL-2 | [23,56,57] |
Blimp-1 | eTreg | Promotes expression of eTreg-related genes | IL-10, KLRG1, Ebi3, CCR6, BCL2 | TCR+CD28+IL-2 | [58] |
Myb | eTreg | Promotes expression of eTreg-related genesin tTreg | ICOS, TIGIT, KLRG1, BCL2, MYC | TCR+CD28+IL-2 | [22] |
RelA | All Tregs | Promotes expression of eTreg-related genes | TIGIT, ST2, KLRG1, CD103, CD30 | TNF-α, GITR | [59,60] |
c-Rel | All Tregs | Promotes expression of eTreg-related genes | TIGIT, ST2, ICOS, EBI3,Blimp-1,IL-10 | Unknown | [59,61] |
Id2 | eTreg | Suppresses Tfr differentiation | CXCR5, IL-10, HIF1-α, IKZF3, Myb, IL-10 rα, E2F2 | TCR+CD28+IL-2 | [62,63,64] |
Id3 | cTreg, CD44lo eTreg | TCR+CD28+IL-2- Erk,PI3K/mTOR | [62,63] | ||
E2A/ HEB | eTreg | Suppresses eTreg differentiation | ICOS, IRF4, CD103, KLRG1, RORγt | TCR+CD28 | [65] |
TCF1/ LEF1 | cTreg, CD44lo eTreg | Regulates Tfr differentiationSuppresses expression of eTreg-related genes? | CD44, ICOS, TIGIT, IRF4, GATA3, Blimp-1, T-bet, Bcl6, CXCR5 | Unknown | [66,67] |
Foxo1 | All Treg | Maintains expression of cTreg-related genes | CD62L, CCR7, Bim, GzmB | TCR+CD28-Akt | [18,68] |
T-bet | eTreg, Tissue Tregs | Regulates migration to Th1-inflammatory sites | CXCR3 | IFNγ-STAT1 | [45,69] |
GATA3 | Skin and Intestinal tTreg | Maintains Treg homeostasis Suppresses skin inflammation | ST2, Foxp3 | TCR, IL-4, IL-33 | [37,70,71] |
RORγt | Intestinal pTreg | Regulates migration to intestinal tissue | CCR6 | IL-6/IL-23-STAT3, Microbiota | [35,36,72] |
BCL6 | Follicular Treg | Regulates Tfr differentiation | CXCR5, PD-1 | IL-21, IL-6 | [73,74] |
c-Maf | eTreg | Regulates RORγτ+ Treg and Tfr differentiations | RORγt, CXCR5, IL-10 | TCR+CD28+IL-2, STAT3, Microbiota, Notch1/2 | [75,76,77] |
STAT3 | All Tregs | Regulates RORγt+ Treg and Tfr differentiation | TCF1, RORγt | IL-6,IL-23,IL-21 | [35,74,75,78,79] |
PPARγ | VAT-Treg | Regulates VAT-Treg differentiation | CCR1, PCYT1A, DGAT1, IL-10 | TCR,IL-33, Adipose tissue-derived factor? | [32,34,44,54] |
RORα | Skin and Colon Tregs | Promotes expression of eTreg-related genes | CCR6, CD73, DR3 | Unknown | [52,80] |
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Koizumi, S.-i.; Ishikawa, H. Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells. Cells 2019, 8, 939. https://doi.org/10.3390/cells8080939
Koizumi S-i, Ishikawa H. Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells. Cells. 2019; 8(8):939. https://doi.org/10.3390/cells8080939
Chicago/Turabian StyleKoizumi, Shin-ichi, and Hiroki Ishikawa. 2019. "Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells" Cells 8, no. 8: 939. https://doi.org/10.3390/cells8080939