Interleukin-1 beta Produced in Response to Islet Autoantigen Presentation Differentiates T-Helper 17 Cells at the Expense of Regulatory T-Cells Implications for the Timing of Tolerizing Immunotherapy
Sebastien Bertin-Maghit, Dimeng Pang, Brendan O'Sullivan, Shannon Best, Emily Duggan, Sanjoy Paul, Helen Thomas, Thomas WH Kay, Leonard C Harrison, Raymond Steptoe, Ranjeny Thomas
Diabetes | AMER DIABETES ASSOC | Published : 2011
OBJECTIVE: The effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelB(lo) DCs, generated in the presence of an nuclear factor-κB inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1β is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1β production and the response to RelB(lo) DCs in the prediabetic period. RESEARCH DESIGN AND METHODS: We injected RelB(lo) DCs su..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Juvenile Diabetes Research Foundation
This work was supported by National Health and Medical Research Council (NHMRC) grants 351439 and 569938 and Juvenile Diabetes Research Foundation grants 1-2006-149 and 5-2003-269. R.T. was supported by Arthritis Queensland and an Australian Research Council Future Fellowship. R.S. was supported by an NHMRC Career Development Award. B.O. was supported by a Queensland Smart State Fellowship.