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/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Aims:  Reactive oxygen species (ROS) are critical in driving the onset of type 1 diabetes (T1D). Ablation of ROS derived from phagocytic NADPH oxidase 2 is protective against autoimmune diabetes in non-obese diabetic (NOD )  mice. However, the mechanisms of NADPH oxidase 2-derived ROS in T1D pathogenesis need to be elucidated. Here, we have examined the role of  Ncf1  (the regulatory subunit of NADPH oxidase 2) in dendritic cells (DC).   Results:   Ncf1 -mutant DCs exhibit reduced ability to activate autoreactive CD8 +  T cells despite no difference in co-stimulatory molecule expression or pro-inflammatory cytokine production. When provided with exogenous whole-protein antigen,  Ncf1 -mutant NOD DCs showed strong phagosome acidification and rapid antigen degradation, which lead to an absence of protein translocation into the cytoplasm and deficient antigenic peptide loading on MHC Class I molecules.   Innovation:  This study demonstrates that Ncf1 (p47 phox ) is required for activation and effector function of CD8 +  T cells by acting both intrinsically within the T cell as well as within professional antigen presenting cells.   Conclusion:  ROS promote CD8 +  T cell activation by facilitating autoantigen cross-presentation by DCs. ROS scavengers could potentially represent an important component of therapies aiming to disrupt autoantigen presentation and activation of CD8 +  T cells in individuals at-risk for developing T1D.

Neutrophil Cytosolic Factor 1 in Dendritic Cells Promotes Autoreactive CD8+ T Cell Activation via Cross-Presentation in Type 1 Diabetes