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Transcriptional regulation of Treg homeostasis and functional specification

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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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  1. Pediatric Diabetes Research Center, Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Ke Wang & Wenxian Fu

  2. Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA

    Wenxian Fu

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  1. Ke Wang
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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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