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

Complement-driven stromal reprogramming in the spleen promotes myelofibrosis, with C3 deficiency or inhibition reducing fibrosis and splenomegaly in mice.

• Why it matters: Understanding how stromal cells contribute to disease progression is crucial for developing targeted therapies for myelofibrosis, especially given the limited current options.
• What they did: The study used spatial and single-cell transcriptomics, imaging, and trajectory analyses on human and mouse spleens to map immune-stromal interactions and identify key pathways involved in disease progression.
• The result: Blocking complement component C3 suppressed inflammatory and fibrotic pathways, restored spleen structure, and decreased disease severity, highlighting complement reprogramming as a promising therapeutic target.