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

作　　者：Min Wang Liu Yang Xiaoyan Sheng Weilei Chen Haiqing Tang Hongguang Sheng Beili Xi Ying Qin Zang 

机构地区：[1]Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China [2]Xuhui Central Hospital, 966 M. Huaihai Road, Shanghai 200031, China

出　　处：《Cell Research》2011年第9期1358-1369,共12页细胞研究（英文版）

摘　　要：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 Thl7 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 yt （RORyt） and signal transducer and activator of transcription 3 （Stat3） phosphorylation. The role of TCV- induced Thl7 suppression was further validated in adoptive transfer experiments with polarized Thl7 cells in subdiabetogenic mice, which was similar to the effect of anti-IL-17 antibody treatment. Collectively our study shows that intrapancreatic Thl7 cell suppression and healthy islet preservation play an important role in the treatment of T1D by TCV.

关 键 词：type 1 diabetes T-cell vaccination Thl 7 intrapanceatic infiltrating lymphocytes 

分 类 号：Q2[生物学—细胞生物学] Q756