Tan, Qiyuan, Tai, Ningwen, Li, Yangyang, Pearson, James  ORCID: https://orcid.org/0000-0002-2867-2269, Pennetti, Sean, Zhou, Zhiguang, Wong, Florence ORCID: https://orcid.org/0000-0002-2812-8845 and Wen, Li
2018.
Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice.
JCI Insight
3
(1)
, 95882.
10.1172/jci.insight.95882
|
Preview |
PDF
- Published Version
Download (3MB) | Preview |
Abstract
B cells play an important role in type 1 diabetes (T1D) development. However, the role of B cell activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized that AID is important in the immunopathogenesis of T1D. To test this hypothesis, we generated AID-deficient (AID–/–) NOD mice. We found that AID–/–NOD mice developed accelerated T1D, with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly, neither maternal IgG transferred through placenta, nor IgA transferred through milk affected the accelerated diabetes development. AID–/–NOD mice showed increased activation and proliferation of B and T cells. We found enhanced T-B cell interactions in AID–/–NOD mice, with increased T-bet and IFN-γ expression in CD4+ T cells in the presence of AID–/– B cells. Moreover, excessive lymphoid expansion was observed in AID–/–NOD mice. Importantly, antigen-specific BDC2.5 CD4+ T cells caused more rapid onset of diabetes when cotransferred with AID–/– B cells than when cotransferred with AID+/+ B cells. Thus, our study provides insights into the role of AID in T1D. Our data also suggest that AID is a negative regulator of immune tolerance and ablation of AID can lead to exacerbated islet autoimmunity and accelerated T1D development.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | American Society for Clinical Investigation |
| ISSN: | 2379-3708 |
| Date of First Compliant Deposit: | 22 January 2018 |
| Date of Acceptance: | 5 December 2017 |
| Last Modified: | 06 May 2023 20:58 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/108328 |
Citation Data
Cited 7 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
 |
Edit Item |
Altmetric
Altmetric