Table 4_Immune cell fibrotic plasticity: mesenchymal-like reprogramming of macrophages, neutrophils and T cells.docx

However, advances in single-cell profiling, spatial analyses and lineage-resolved approaches are beginning to challenge this rigid division of cellular labour. Emerging evidence indicates that, in persistently injured and maladaptively repairing tissues, selected immune cell populations can acquire matrix producing, cytoskeletal remodelling and mesenchymal-like functions, thereby contributing more directly to structural tissue remodelling.

In this Review, we introduce the concept of immune cell fibrotic plasticity and critically assess the evidence, regulatory mechanisms and pathological significance of fibrotic effector states in macrophages, neutrophils and T cells. Macrophage reprogramming towards myofibroblast-like states appears to be shaped by convergent TGF-β/SMAD signalling, metabolic adaptation and epigenetic regulation. Neutrophils can synthesize, transport and organize extracellular matrix, conferring temporally distinct functions in tissue stabilization and pathological scarring.