KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties - UNICANCER Access content directly
Journal Articles Science Advances Year : 2023

KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties

Saba Nayar
Sylvain Baulande
Mylène Bohec
Francesca Barone
  • Function : Author

Abstract

Mature lymphoid stromal cells (LSCs) are key organizers of immune responses within secondary lymphoid organs. Similarly, inflammation-driven tertiary lymphoid structures depend on immunofibroblasts producing lymphoid cytokines and chemokines. Recent studies have explored the origin and heterogeneity of LSC/immunofibroblasts, yet the molecular and epigenetic mechanisms involved in their commitment are still unknown. This study explored the transcriptomic and epigenetic reprogramming underlying LSC/immunofibroblast commitment. We identified the induction of lysine demethylase 6B (KDM6B) as the primary epigenetic driver of early immunofibroblast differentiation. In addition, we observed an enrichment for KDM6B gene signature in murine inflammatory fibroblasts and pathogenic stroma of patients with autoimmune diseases. Last, KDM6B was required for the acquisition of LSC/immunofibroblast functional properties, including the up-regulation of CCL2 and the resulting recruitment of monocytes. Overall, our results reveal epigenetic mechanisms that participate in the early commitment and immune properties of immunofibroblasts and support the use of epigenetic modifiers as fibroblast-targeting strategies in chronic inflammation.

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hal-04328598 , version 1 (07-12-2023)

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Attribution - NonCommercial

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Marvin Sylvestre, Nicolas Barbier, Vonick Sibut, Saba Nayar, Céline Monvoisin, et al.. KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties. Science Advances , 2023, Science Advances, 9 (48), pp.eadh2708. ⟨10.1126/sciadv.adh2708⟩. ⟨hal-04328598⟩
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