CD25 signaling regulates the function and stability of peripheral Foxp3+ regulatory T cells derived from the spleen and lymph nodes of mice

Kunpeng Wang; Jian Gu; Xuhao Ni; Zheng Ding; Qi Wang; Haoming Zhou; SongGuo Zheng; Bin Li; Ling Lu

doi:10.1016/j.molimm.2016.06.007

CD25 signaling regulates the function and stability of peripheral Foxp3+ regulatory T cells derived from the spleen and lymph nodes of mice

Mol Immunol. 2016 Aug:76:35-40. doi: 10.1016/j.molimm.2016.06.007. Epub 2016 Jun 23.

Authors

Kunpeng Wang¹, Jian Gu¹, Xuhao Ni¹, Zheng Ding¹, Qi Wang¹, Haoming Zhou¹, SongGuo Zheng², Bin Li³, Ling Lu⁴

Affiliations

¹ Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
² Division of Rheumatology, Penn State Hershey College of Medicine, Hershey, PA 17033, USA.
³ Key Laboratory of Molecular Virology & Immunology, CAS Center for Excellence in Molecular Cell Science, Unit of Molecular Immunology, Institute Pasteur of Shanghai, University of Chinese Academy of Sciences, Shanghai 200031, China.
⁴ Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. Electronic address: lvling@njmu.edu.cn.

PMID: 27344615
DOI: 10.1016/j.molimm.2016.06.007

Abstract

Regulatory T cells (Tregs) play a critical role in sustaining immune tolerance and maintaining immune balance to alloantigen after transplatation. However, the functions of peripheral Tregs in different organs have not been fully characterized. Here, we showed that spleen-derived Tregs exhibited higher expression of Foxp3, greater suppressive capacity, and lower levels of IL-17A secretion than lymph node-derived Tregs in vitro in the presence or absence of inflammatory cytokines, such as IL-6. We found a higher percentage of CD25(bright) Tregs among spleen-derived Tregs than among lymph node-derived Tregs. Additionally, in vivo experiments demonstrated that adoptive transfer of spleen-derived Tregs, but not lymph node-derived Tregs, alleviated ischemia-reperfusion injury. These results reveal novel functions of Tregs derived from peripheral organs. In particular, spleen-derived Tregs, primarily consisting of CD25(bright) cells, may provide a more significant contribution to the suppression of immune-mediated autoimmune and inflammatory disease.

Keywords: CD25; Foxp3; IL-17; IR; Treg.

Publication types

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

MeSH terms

Animals
Disease Models, Animal
Fluorescent Antibody Technique
Forkhead Transcription Factors / immunology
Gene Knock-In Techniques
Interleukin-2 Receptor alpha Subunit / immunology*
Lymph Nodes / cytology
Lymph Nodes / immunology
Mice
Mice, Inbred C57BL
Reperfusion Injury / immunology
Signal Transduction / immunology
Spleen / cytology
Spleen / immunology*
T-Lymphocyte Subsets / immunology*
T-Lymphocytes, Regulatory / immunology*

Substances

Forkhead Transcription Factors
Foxp3 protein, mouse
Il2ra protein, mouse
Interleukin-2 Receptor alpha Subunit