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 Plus

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

Zendy Tools

Zendy Open

Objective  Injury‐associated axon‐intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis ( MS ). Retrograde interferon gamma ( IFN  γ ) signals are known to induce expression of major histocompatibility class I ( MHC  I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen‐specific  CD 8 +  T cells. We sought to determine whether the same is true in human neurons.    Methods  A novel microisolation chamber design was used to physically isolate and manipulate axons from human skin fibroblast‐derived induced pluripotent stem cell ( iPSC )‐derived neuron‐enriched neural aggregates. Fluorescent retrobeads were used to assess the fraction of neurons with projections to the distal chamber. Axons were treated with  IFN  γ  for 72 h and expression of  MHC  class I and antigen presentation genes were evaluated by  RT ‐ PCR  and immunofluorescence.    Results  Human  iPSC ‐derived neural stem cells maintained as 3D aggregate cultures in the cell body chamber of polymer microisolation chambers extended dense axonal projections into the fluidically isolated distal chamber. Treatment of these axons with  IFN  γ  resulted in upregulation of  MHC  class I and antigen processing genes in the neuron cell bodies.  IFN  γ ‐induced  MHC  class I molecules were also anterogradely transported into the distal axon.    Interpretation  These results provide conclusive evidence that human axons are competent to express  MHC  class I molecules, suggesting that inflammatory factors enriched in demyelinated lesions may render axons vulnerable to attack by autoreactive  CD 8 +  T cells in patients with  MS . Future work will be aimed at identifying pathogenic anti‐axonal T cells in these patients.

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons