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.

journal_name

Cell Res

journal_title

Cell research

authors

Wang M,Yang L,Sheng X,Chen W,Tang H,Sheng H,Xi B,Zang YQ

doi

10.1038/cr.2011.74

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

1358-69

issue

9

eissn

1001-0602

issn

1748-7838

pii

cr201174

journal_volume

21

pub_type

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