Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice
| Autor: | Qiyuan Tan, Ningwen Tai, Yangyang Li, F. Susan Wong, Sean Pennetti, Zhiguang Zhou, Li Wen, James A. Pearson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Placenta T-Lymphocytes Autoimmunity Adaptive Immunity medicine.disease_cause Immune tolerance Mice 0302 clinical medicine Mice Inbred NOD Pregnancy Activation-induced (cytidine) deaminase Insulin NOD mice B-Lymphocytes Virulence biology Chemistry General Medicine Cytidine deaminase Acquired immune system Milk medicine.anatomical_structure Gene Knockdown Techniques Cytokines Female Research Article Interferon-gamma 03 medical and health sciences Cytidine Deaminase Immune Tolerance medicine Animals B cell Autoantibodies medicine.disease R1 Immunoglobulin A Enzyme Activation Diabetes Mellitus Type 1 030104 developmental biology Immunoglobulin G Immunology biology.protein Lymph Nodes Insulitis Spleen 030215 immunology |
| ISSN: | 2379-3708 |
| Popis: | B cells play an important role in type 1 diabetes (T1D) development. However, the role of B cell\ud activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized\ud that AID is important in the immunopathogenesis of T1D. To test this hypothesis, we generated\ud AID-deficient (AID–/–) NOD mice. We found that AID–/–NOD mice developed accelerated T1D,\ud with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly,\ud neither maternal IgG transferred through placenta, nor IgA transferred through milk affected the\ud accelerated diabetes development. AID–/–NOD mice showed increased activation and proliferation\ud of B and T cells. We found enhanced T-B cell interactions in AID–/–NOD mice, with increased T-bet\ud and IFN-γ expression in CD4+ T cells in the presence of AID–/– B cells. Moreover, excessive lymphoid\ud expansion was observed in AID–/–NOD mice. Importantly, antigen-specific BDC2.5 CD4+ T cells\ud caused more rapid onset of diabetes when cotransferred with AID–/– B cells than when cotransferred\ud with AID+/+ B cells. Thus, our study provides insights into the role of AID in T1D. Our data also\ud suggest that AID is a negative regulator of immune tolerance and ablation of AID can lead to\ud exacerbated islet autoimmunity and accelerated T1D development. |
| Databáze: | OpenAIRE |
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