The Innate and Adaptive Immune Functions of Osteoblast-Lineage Cells

The osteoblast lineage has traditionally been viewed through a structural and metabolic lens, yet growing evidence indicates that these cells possess diverse functions, including roles in innate and adaptive immune responses. To establish a coherent mechanistic framework, we performed a systematic review of the literature concerning immune signalling, antigen presentation, and pathogen responses across the osteoblast lineage.

We identified 463 unique studies, with 43 meeting the inclusion criteria. Our synthesis reveals a stage-specialised immune continuum. Osteoprogenitors appear to initiate early inflammatory signalling while mature osteoblasts operate as microbial sensors and conditional antigen-presenting cells via inducible expression of cell membrane and cytosolic pattern recognition receptors, and a functional major histocompatibility complex class II apparatus. Osteocytes, the most abundant and long-lived bone cell type, are also capable of detecting microbial danger and activate extensive interferon, chemokine and cytokine programmes within the lacunocanalicular network. Together, these properties define a stromal immune system that coordinates both innate and adaptive immunity across bone surfaces and the mineralised matrix. This osteoblast lineage-integrated immune architecture provides a conceptual basis for understanding osteomyelitis incidence and persistence, biomaterial-immune interactions, as well as inflammatory bone remodelling, reframing this lineage as a previously underappreciated regulator of skeletal and systemic immunity.