In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 128.18-128.18
Abstract:
Viruses are important in the pathogenesis of type 1 diabetes mellitus (T1DM). A pancreatrophic strain of coxsackievirus, CVB4, which is associated with the development of T1DM in humans, accelerates the development of T1DM in NOD mice. Toll-Like Receptor 3 (TLR3) is activated by viral dsRNA and is broadly expressed by NOD mice and human pancreatic beta cells, suggesting that TLR3 signaling may be important in CVB4 acceleration of T1DM. We used NOD mice deficient in TLR3 (TLR3 KO) to test the hypothesis that TLR3 signaling is important in CVB4 acceleration of T1DM in NOD mice. We report that TLR3 KO NOD mice are markedly protected from CVB4 acceleration of T1DM compared to wild type (WT) NOD mice. Similarly, we have observed that phenylmethimazole (C10), which has recently been shown to inhibit dsRNA-triggered TLR3 signaling, also delays CVB4 acceleration of T1DM in NOD mice. In preliminary experiments to investigate the mechanism by which TLR3 deficiency provides protection from T1DM in this model, we observed marked differences in T regulatory cell populations between TLR3 KO and WT NOD mice, and a significant enhancement of viral clearance in C10-treated NOD mice. These results indicate the distinct importance of TLR3 signaling in environmental (i.e. viral) induction of T1DM and that C10 could potentially protect β cells from virus-induced insulitis.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.128.18
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
