Aire-Overexpressing Dendritic Cells Induce Peripheral CD4+ T Cell Tolerance

Li, Dongbei; Li, Haijun; Fu, Haiying; Niu, Kunwei; Guo, Yantong; Guo, Chuan; Sun, Jitong; Li, Yi; Yang, Wei

doi:10.3390/ijms17010038

Open AccessArticle

Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance

by

Dongbei Li

^†,

Haijun Li

^†,

Haiying Fu

,

Kunwei Niu

,

Yantong Guo

,

Chuan Guo

,

Jitong Sun

,

Yi Li

^* and

Wei Yang

^*

Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2016, 17(1), 38; https://doi.org/10.3390/ijms17010038

Submission received: 30 October 2015 / Revised: 14 December 2015 / Accepted: 18 December 2015 / Published: 29 December 2015

(This article belongs to the Section Biochemistry)

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Abstract

Autoimmune regulator (Aire) can promote the ectopic expression of peripheral tissue-restricted antigens (TRAs) in thymic medullary epithelial cells (mTECs), which leads to the deletion of autoreactive T cells and consequently prevents autoimmune diseases. However, the functions of Aire in the periphery, such as in dendritic cells (DCs), remain unclear. This study’s aim was to investigate the effect of Aire-overexpressing DCs (Aire cells) on the functions of CD4⁺ T cells and the treatment of type 1 diabetes (T1D). We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4⁺ T cells in STZ-T1D mouse-derived splenocytes. Furthermore, following insulin stimulation, Aire cells decreased the number of CD4⁺ IFN-γ⁺ T cells in both STZ-T1D and WT mouse-derived splenocytes and reduced the expression levels of TCR signaling molecules (Ca²⁺ and p-ERK) in CD4⁺ T cells. We observed that Aire cells-induced CD4⁺ T cells could delay the development of T1D. In summary, Aire-expressing DCs inhibited TCR signaling pathways and decreased the quantity of CD4⁺IFN-γ⁺ autoreactive T cells. These data suggest a mechanism for Aire in the maintenance of peripheral immune tolerance and provide a potential method to control autoimmunity by targeting Aire.

Keywords: Aire; DCs; CD4⁺T cells; T1D

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MDPI and ACS Style

Li, D.; Li, H.; Fu, H.; Niu, K.; Guo, Y.; Guo, C.; Sun, J.; Li, Y.; Yang, W. Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance. Int. J. Mol. Sci. 2016, 17, 38. https://doi.org/10.3390/ijms17010038

AMA Style

Li D, Li H, Fu H, Niu K, Guo Y, Guo C, Sun J, Li Y, Yang W. Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance. International Journal of Molecular Sciences. 2016; 17(1):38. https://doi.org/10.3390/ijms17010038

Chicago/Turabian Style

Li, Dongbei, Haijun Li, Haiying Fu, Kunwei Niu, Yantong Guo, Chuan Guo, Jitong Sun, Yi Li, and Wei Yang. 2016. "Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance" International Journal of Molecular Sciences 17, no. 1: 38. https://doi.org/10.3390/ijms17010038

APA Style

Li, D., Li, H., Fu, H., Niu, K., Guo, Y., Guo, C., Sun, J., Li, Y., & Yang, W. (2016). Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance. International Journal of Molecular Sciences, 17(1), 38. https://doi.org/10.3390/ijms17010038

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Aire-Overexpressing Dendritic Cells Induce Peripheral CD4⁺ T Cell Tolerance

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