Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 6; pp. 1702 - 1708.e5
• Main Authors: Yang, Gui, MD, Geng, Xiao-Rui, MD, Song, Jiang-Ping, MD, PhD, Wu, Yingying, PhD, Yan, Hao, MS, Zhan, Zhengke, MS, Yang, Litao, PhD, He, Weiyi, MS, Liu, Zhi-Qiang, MD, PhD, Qiu, Shuqi, MD, Liu, Zhigang, MD, PhD, Yang, Ping-Chang, MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2014; Elsevier; Elsevier Limited
• Subjects: Adoptive Transfer; Adult; Allergic diseases; allergy; Allergy and Immunology; Animals; Biological and medical sciences; Cell growth; Digestive allergic diseases; Disease Models, Animal; Female; Flow cytometry; Food Hypersensitivity - genetics; Food Hypersensitivity - immunology; Food Hypersensitivity - metabolism; Forkhead Transcription Factors - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Gene Silencing; Human subjects; Humans; Immunopathology; Immunophenotyping; insulin-like growth factor; Insulin-Like Growth Factor II - metabolism; Insulin-like growth factors; intestine; Intestines - immunology; Intestines - metabolism; Intestines - pathology; Kinases; Lymphocyte Activation - immunology; Lymphocytes; Male; Medical sciences; Methods; Mice; Phenotype; Receptor, IGF Type 2 - genetics; Receptor, IGF Type 2 - metabolism; Regulation; Regulatory T cell; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T cell receptors; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; transforming growth factor; Young Adult; China; Carboxyfluorescein diacetate succinimidyl ester; TCR; intestine; iTreg; T-cell receptor; Forkhead box protein 3; shRNA; Inducible regulatory T; Regulatory T; insulin-like growth factor; Lamina propria mononuclear cell; Insulin-like growth factor 2 receptor; Ovalbumin; Treg; Extracellular signal-regulated kinase; Mitogen-activated protein kinase; allergy; IGF; Small hairpin RNA; CFSE; Effector T; MAPK; IGF2R; Teff; Regulatory T cell; LPMC; OVA; transforming growth factor; Foxp3; ERK; Food allergy; Immunopathology; Digestive system; Transforming growth factor; Gut; Experimental study; Insulin like growth factor 2; Insulin like growth factor; Immunology; T-Lymphocyte; Digestive diseases; Models; Regulatory cell
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2014.02.019

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. Objectives 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.