Le 30 July 2020

Article publié : Implication de la voie JAK/STAT dans la maladie de Takayasu, une nouvelle piste thérapeutique !

Le 30 July 2020

Article publié : Implication de la voie JAK/STAT dans la maladie de Takayasu, une nouvelle piste thérapeutique !

Notre équipe a publié un article sur l’implication de la voie JAK/STAT dans la physiopathologie de la maladie de Takayasu. De nouvelles pistes thérapeutiques sont envisageables (Inhibiteurs de JAK : ruxolitinib, tofacitinib, baracitinib etc…)

Résumé: 

Objective: Takayasu’s arteritis (TAK) is a large vessel vasculitis with important infiltration of proinflammatory T cells in the aorta and its main branches, but its aetiology is still unknown. Our work aims to explore the involvement of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signalling pathway in proinflammatory T cells differentiation and disease activity of TAK.

Methods: We analysed transcriptome and interferons gene signatures of fluorescence-activated cell sorting (FACS-sorted) CD4+ and CD8+ T cells from healthy donors (HD) and in 25 TAK (median age of 37.6 years including 21 active TAK with National Institutes of Health (NIH) score >1). Then we tested, in vitro and in vivo, the effects of JAK inhibitors (JAKinibs) in TAK.

Results: Transcriptome analysis showed 248 and 432 significantly dysregulated genes for CD4+ and CD8+ samples between HD and TAK, respectively. Among dysregulated genes, we highlighted a great enrichment for pathways linked to type I and type II interferons, JAK/STAT and cytokines/chemokines-related signalling in TAK. We confirmed by Real Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) the upregulation of type I interferons gene signature in TAK as compared with HD. JAKinibs induced both in vitro and in vivo a significant reduction of CD25 expression by CD4+ and CD8+ T cells, a significant decrease of type 1 helper T cells (Th1) and Th17 cells and an increase of Tregs cells in TAK. JAKinibs also decreased C reactive protein level, NIH score and corticosteroid dose in TAK patients.

Conclusions: JAK/STAT signalling pathway is critical in the pathogenesis of TAK and JAKinibs may be a promising therapy.

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