KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
medline:
1
12
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38019914
doi: 10.1126/sciadv.adh2708
pmc: PMC10686565
doi:
Substances chimiques
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
KDM6B protein, human
EC 1.14.11.-
Kdm6b protein, mouse
EC 1.5.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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