Requirement for POH1 in differentiation and maintenance of regulatory T cells

Yun Liu; Li Zhang; Boshi Wang; Zhaojuan Yang; Guiqin Xu; Aihui Ma; Ming Tang; Tiantian Jing; Lin Wu; Xiaoli Xu; Yongzhong Liu

doi:10.1038/s41418-018-0162-z

Requirement for POH1 in differentiation and maintenance of regulatory T cells

Cell Death Differ. 2019 Mar;26(4):751-762. doi: 10.1038/s41418-018-0162-z. Epub 2018 Jul 23.

Authors

Yun Liu^#¹, Li Zhang^#¹, Boshi Wang¹, Zhaojuan Yang¹, Guiqin Xu¹, Aihui Ma¹, Ming Tang¹, Tiantian Jing¹, Lin Wu¹, Xiaoli Xu¹, Yongzhong Liu²

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China. [email protected].

^# Contributed equally.

Abstract

Foxp3-expressing regulatory T (Treg) cells are essential for averting autoimmune diseases and maintaining immune homeostasis. However, the molecular mechanisms underlying the development and maintenance of Treg cells are still unclear. Here, we found that T cell-specific deletion of the gene encoding the deubiquitinase POH1 compromised the development of mature T cells, especially CD4⁺Foxp3⁺ Treg cells. Moreover, POH1 deficiency significantly attenuated the transition of CD25⁺ Treg cell precursors into Foxp3⁺ Treg cells accompanied by downregulation of interleukin 2 (IL-2)-STAT5 signaling. Deletion of POH1 in generated CD4⁺Foxp3⁺ Treg cells led to an early onset of fetal autoimmune disorders and a decrease in the pool size of peripheral Treg cells in mice, which were mostly due to decreased expansion of these cells. Thus, these results revealed that POH1 has a pivotal role in the development and maintenance of CD4⁺Foxp3⁺ Treg cells and contributes to immune tolerance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmunity / genetics*
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
Cell Differentiation / genetics*
Cell Differentiation / immunology
Cell Proliferation / genetics
Forkhead Transcription Factors / immunology
Forkhead Transcription Factors / metabolism*
Immune Tolerance / genetics*
Interleukin-2 / metabolism
Interleukin-2 Receptor alpha Subunit / immunology
Interleukin-2 Receptor alpha Subunit / metabolism
Lymph Nodes / immunology
Lymph Nodes / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism*
RNA-Seq
STAT5 Transcription Factor / metabolism
Spleen / immunology
Spleen / metabolism
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism*
Thymus Gland / immunology
Thymus Gland / metabolism
Trans-Activators / genetics
Trans-Activators / metabolism*

Substances

Forkhead Transcription Factors
Foxp3 protein, mouse
Il2ra protein, mouse
Interleukin-2
Interleukin-2 Receptor alpha Subunit
PSMD14 protein, mouse
STAT5 Transcription Factor
Trans-Activators
Proteasome Endopeptidase Complex