Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model.
BACKGROUND
The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet.


OBJECTIVE
We sought to investigate the role of insulin-like growth factor (IGF) 2 in the upregulation of Treg cell function.


METHODS
The expression of insulin-like growth factor 2 receptor (IGF2R) on T cells was assessed by using flow cytometry. Treg cell functions were evaluated by assessing the suppressor effect on proliferation of other effector T (Teff) cells. The effect of IGF2 on regulating Treg cell functions were evaluated with a cell-culture model and a food allergy mouse model.


RESULTS
Expression of IGF2R was observed in more than 90% of murine and human Treg cells but in less than 10% of effector CD4(+) T cells. Activation of IGF2R and T-cell receptor induced marked Treg cell proliferation and release of TGF-β from Treg cells, which enhanced Treg cell immune suppressor effects on other Teff cell activities and allergic inflammation in the intestine.


CONCLUSIONS
Activation of IGF2R enhances Treg cell functions in suppressing other Teff cell activities and inhibiting allergic inflammation in the intestine.
ENT Institute of Shenzhen University, Shenzhen, China; Longgang Central Hospital, Shenzhen ENT Institute, Shenzhen, China.
Gui
G
Yang
ENT Institute of Shenzhen University, Shenzhen, China; Longgang Central Hospital, Shenzhen ENT Institute, Shenzhen, China.
Xiao-Rui
XR
Geng
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jiang-Ping
JP
Song
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Yingying
Y
Wu
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Hao
H
Yan
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Zhengke
Z
Zhan
ENT Institute of Shenzhen University, Shenzhen, China; Longgang Central Hospital, Shenzhen ENT Institute, Shenzhen, China.
Litao
L
Yang
State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Weiyi
W
He
ENT Institute of Shenzhen University, Shenzhen, China; Longgang Central Hospital, Shenzhen ENT Institute, Shenzhen, China.
Zhi-Qiang
ZQ
Liu
ENT Institute of Shenzhen University, Shenzhen, China; Longgang Central Hospital, Shenzhen ENT Institute, Shenzhen, China.
Shuqi
S
Qiu
ENT Institute of Shenzhen University, Shenzhen, China; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address: lzg@szu.edu.cn.
Zhigang
Z
Liu
ENT Institute of Shenzhen University, Shenzhen, China; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address: pcy2356@szu.edu.cn.
Ping-Chang
PC
Yang
D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D016130:Immunophenotyping; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D010641:Phenotype; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
D051858:Forkhead Transcription Factors; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II
Regulatory T cell; allergy; insulin-like growth factor; intestine; transforming growth factor