title: T-cell vaccination leads to suppression of intrapancreatic Th17 cells through Stat3-mediated RORγt inhibition in autoimmune diabetes.
abstract: 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.
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sheng
authors.forename: Weilei
authors.initials: W
authors.lastname: Chen
authors.forename: Haiqing
authors.initials: H
authors.lastname: Tang
authors.forename: Hongguang
authors.initials: H
authors.lastname: Sheng
authors.forename: Beili
authors.initials: B
authors.lastname: Xi
authors.forename: Ying Qin
authors.initials: YQ
authors.lastname: Zang
mesh_terms: D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014611:Vaccination
chemical_list: D007328:Insulin; D020381:Interleukin-17; D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor