Abstract
CD4+Foxp3+ regulatory T (Treg) cells are key players in keeping excessive inflammation in check. Mounting evidence has shown that Treg cells exert much more diverse functions in both immunological and non-immunological processes. The development, maintenance and functional specification of Treg cells are regulated by multilayered factors, including antigens and TCR signaling, cytokines, epigenetic modifiers and transcription factors (TFs). In the review, we will focus on TFs by summarizing their unique and redundant roles in Treg cells under physiological and pathophysiological conditions. We will also discuss the recent advances of Treg trajectories between lymphoid organs and non-lymphoid tissues. This review will provide an updated view of the newly identified TFs and new functions of known TFs in Treg biology.
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Abbreviations
- AhR:
-
Aryl hydrocarbon receptor
- Akt:
-
AKT serine/threonine kinase 1
- AP1:
-
Activator protein 1
- ATF:
-
Activating transcription factor
- Bach2:
-
BTB domain and CNC homolog 2
- BATF:
-
Basic leucine zipper ATF-like transcription factor
- Bcl10:
-
B-cell lymphoma/leukemia 10
- Bcl11b:
-
B-cell lymphoma/leukemia 11b
- Bcl6:
-
B-cell lymphoma/leukemia 6
- Blimp1:
-
B-lymphocyte-induced maturation protein 1
- CARD11:
-
Caspase recruitment domain family member 11
- Cbfβ:
-
Core-binding factor subunit beta
- c-Maf:
-
V-maf musculoaponeurotic fibrosarcoma oncogene homolog
- CREB:
-
CAMP responsive element binding protein 1
- c-Rel:
-
REL proto-oncogene, NF-κB subunit
- CTLA4:
-
Cytotoxic T-lymphocyte associated protein 4
- DOCK8:
-
Dedicator of cytokinesis 8
- E47:
-
Transcription factor 3
- Eos:
-
IKAROS family zinc finger 4
- EZH2:
-
Enhancer of Zeste homolog 2
- Foxo1:
-
Forkhead box O1
- Foxo3:
-
Forkhead box O3
- Foxp1:
-
Forkhead box P1
- Foxp3:
-
Forkhead box P3
- GATA1:
-
GATA binding protein 1
- GATA3:
-
GATA binding protein 3
- Helios:
-
IKAROS family zinc finger 2
- HIF1α:
-
Hypoxia inducible factor 1 subunit alpha
- Id3:
-
Inhibitor of DNA binding 3, HLH protein
- IKKβ:
-
Inhibitor of nuclear factor kappa B kinase subunit beta
- IRF4:
-
Interferon regulatory factor 4
- IκB:
-
Inhibitor of nuclear factor kappa B
- JunB:
-
JunB proto-oncogene, AP-1 transcription factor subunit
- Klrg1:
-
Killer cell lectin like receptor G1
- LEF1:
-
Lymphoid enhancer binding factor 1
- MALT1:
-
Mucosa-associated lymphoid tissue lymphoma translocation protein 1
- NFAT:
-
Nuclear factor of activated T cells
- Nfil3:
-
Nuclear factor, interleukin 3 regulated
- NF-κB:
-
Nuclear factor kappa B subunit 1
- Nr4a:
-
Nuclear receptor subfamily 4 group A
- PPARγ:
-
Peroxisome proliferator-activated receptor gamma
- Rbpj:
-
Recombination signal binding protein for immunoglobulin kappa J region
- RelA:
-
RELA proto-oncogene, NF-κB subunit
- RORγt:
-
RAR-related orphan receptor gamma
- Runx1:
-
RUNX family transcription factor 1
- Satb1:
-
SATB homeobox 1
- SMAD:
-
Sma- and mad-related protein
- SOCS1:
-
Suppressor of cytokine signaling 1
- SOCS3:
-
Suppressor of cytokine signaling 3
- Spi-B:
-
Spi-B transcription factor
- STAT5:
-
Signal transducer and activator of transcription 5
- T-bet:
-
T-box expressed in T cells
- TCF1:
-
T-cell factor 1
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Acknowledgements
We thank the Fu lab members for insightful discussions. This work was funded by the US National Institute of Health (AI139753 to W.F.). We apologize to those individuals whose work could not be cited here due to space limitation.
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Conceptualization: KW and WF. Writing and editing: KW and WF
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Wang, K., Fu, W. Transcriptional regulation of Treg homeostasis and functional specification. Cell. Mol. Life Sci. 77, 4269–4287 (2020). https://doi.org/10.1007/s00018-020-03534-7
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DOI: https://doi.org/10.1007/s00018-020-03534-7