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

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

Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China
These authors contributed equally to this work.
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Authors to whom correspondence should be addressed.
Academic Editor: J. Michael Wyss
Received: 30 October 2015 / Revised: 14 December 2015 / Accepted: 18 December 2015 / Published: 29 December 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: Aire; DCs; CD4+T cells; T1D Aire; DCs; CD4+T cells; T1D
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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.

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