The CD27–CD70 axis in osteoclast development

The engagement of CD70 on dendritic cells (DCs) and lymphocytes by CD27 sustains immune activation. Here, the CD27–CD70 axis is shown to also impede osteoclast development in the bone marrow. Cd27^+/− mice that constitutively express a Cd70 transgene on DCs had increased trabecular bone mass compared with Cd27^+/+ mice because of defective osteoclast differentiation. Osteoclast progenitors could be classified into a CD27^hi subset, which could generate both osteoclasts and DCs, and a CD27^low subset, which was fully commited to the osteoclast lineage. Constitutive CD70 signalling skewed osteoclast progenitors towards DC differentiation, which led to the defective development of osteoclasts. It will be interesting to assess whether chronic immune activation (including constitutive CD70 signalling) also affects the function of other haematopoietic progenitor cells in the bone marrow.