The IL-33/ST2 Axis Promotes Traumatic Heterotopic Ossification by Driving Macrophage and Mast Cell-Mediated Inflammation via Autophagy Defects.

ABSTRACT: Trauma-induced Heterotopic ossification (tHO) is the abnormal osteogenesis occurring in soft tissues after traumatic musculoskeletal injury, which can lead to severe limb movement impairment or even disability. Recent studies have indicated that macrophages and mast cells play a crucial role in tHO, although their precise activation mechanism remained to be elusive. Here, we unveil a novel mechanism in which interleukin-33 (IL-33)-an alarmin in the mammalian innate immune response to trauma-rapidly increases upon tendon injury and binds to its receptor ST2 (IL-1RL1) on macrophages and mast cells. This binding initiates M2 polarization in macrophages and degranulation in mast cells, thereby promoting osteogenic differentiation during tHO formation. Mechanistically, the IL-33/ST2 axis leads

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12681708 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature