Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement‑driven immune‑stromal interactions as a therapeutic target.

Rákkutatás · Myelofibrosis

Non‑hematopoietic complement component C3 deficiency or pharmacological C3 inhibition suppresses these pathways, restores splenic architecture, and reduces splenomegaly and bone marrow fibrosis.

The study mapped splenic mesenchymal stromal niches in myelofibrosis using spatial and single‑nucleus transcriptomics, imaging, and trajectory analyses. It showed that reticular cells transition from hematopoiesis‑supportive to inflammatory and pro‑fibrotic states driven by macrophage‑ and megakaryocyte‑derived signals that activate complement and induce TNF‑α, TGF‑β, ECM, and Thbs1 programs. Deficiency or pharmacological inhibition of complement component C3 suppressed these pathways, restored splenic architecture, and reduced splenomegaly and bone marrow fibrosis.

The data identify complement‑dependent stromal reprogramming as a mechanism that drives extramedullary hematopoiesis and fibrosis in myelofibrosis, providing a potential therapeutic target.

Bizonyítékszint: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

Eredeti forrás

Kapcsolódó jelek