Volume 21, No 9, Sep 2011

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 21 Issue 9, September 2011: 1358-1369

ORIGINAL ARTICLES

T-cell vaccination leads to suppression of intrapancreatic Th17 cells through Stat3-mediated RORγt inhibition in autoimmune diabetes

Min Wang¹, Liu Yang¹, Xiaoyan Sheng¹, Weilei Chen¹, Haiqing Tang¹, Hongguang Sheng², Beili Xi² and Ying Qin Zang¹

¹Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China;

²Xuhui Central Hospital, 966 M. Huaihai Road, Shanghai 200031, China Correspondence: Ying Qin Zanga, Beili Xi,(yqin@sibs.ac.cn; xi.beili@hotmail.com)

Immunization with inactivated autoreactive T cells is an effective therapeutic approach to ameliorating autoimmune diseases, while the underlying mechanisms that regulate autoreactive T cells are not completely understood. This study tested the hypothesis that T-cell vaccination (TCV) inhibits autoimmune diabetes in mice through the suppression of Th17 cells. The results showed that TCV treatment decreased hyperglycemia in type 1 diabetes (T1D) induced by multiple low-dose streptozotocin (MLD-STZ) as compared with the controls, preserved the number of healthy pancreatic islets and increased the production of insulin in the islets. Further study revealed that TCV significantly decreased the production of both interleukin (IL)-17 and IL-23 in intrapancreatic infiltrating lymphocytes (IPL) through marked inhibition of mRNA level of retinoic acid-related orphan receptor γt (RORγt) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. The role of TCV-induced Th17 suppression was further validated in adoptive transfer experiments with polarized Th17 cells in sub-diabetogenic mice, which was similar to the effect of anti-IL-17 antibody treatment. Collectively our study shows that intrapancreatic Th17 cell suppression and healthy islet preservation play an important role in the treatment of T1D by TCV.

Cell Research (2011) 21:1358-1369. doi:10.1038/cr.2011.74; published online 26 April 2011

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