English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

TNF-α has been linked to the development of type 1 diabetes (T1D). We previously reported that neonatal treatment of nonobese diabetic (NOD) mice with TNF-α accelerated the onset of T1D, whereas TNF-α blockade in the same time period resulted in a complete absence of diabetes. The mechanisms by which TNF-α modulates development of T1D in NOD mice remain unclear. Here we tested the effects of TNF-α on the maturation of dendritic cells (DCs) in the NOD mouse. We found that neonatal treatment with TNF-α caused an increase in expression of maturation markers on CD11c+ CD11b+ DC subpopulations, whereas treatment with anti-TNF-α resulted in a decrease in expression of maturation markers in the CD11c+ CD11b+ subset. Moreover, neonatal treatment with TNF-α resulted in skewed development of a CD8α+ CD11b- CD11c+ DC subset such that TNF-α decreases the CD8α+ CD11c+ DC subset, increases the CD11c+ CD11b+ subset, and causes an increase in the expression of CD40 and CD54 on mature DCs capable of inducing immunity. Anti-TNF-α-treated mice had an increase in the CD8α+ CD11c+ DCs. Notably, adoptively transferred naïve CD4+ T cells from BDC2.5 T cell receptor transgenic mice proliferated in the pancreatic lymph nodes in TNF-α-treated NOD mice but not in anti-TNF-α-treated mice. Finally, we show that anti-TNF-α-treated mice showed immunological tolerance to islet cell proteins. We conclude that TNF-α plays an important role in the initiation of T1D in the NOD mouse by regulating the maturation of DCs and, thus, the activation of islet-specific pancreatic lymph node T cells.

The role of TNF-α in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation