A hypothetic model of the mechanism by which PSTPIP2 deficiency in cmo mice primes the innate immune system for exaggerated and prolonged inflammatory responses. Before disease onset (solid lines), cmo mice produce increased numbers of primitive myeloid progenitors (HPP-CFC) in the BM that migrate to the spleen, where they either become resident HPP-CFCs or differentiate into CFU-M. Tissue damage (dashed lines) induces increased production of MIP-1α and IL-6 by tissue macrophages. IL-6 promotes the proliferation of splenic HPP-CFC, and MIP-1α increases the recruitment of circulating (pro-) monocytes to peripheral tissues (), thus establishing a positive feedback loop. MIP-1α and IL-6 also promote the recruitment of osteoclast precursors and osteoclastogenesis, leading to inflammatory bone resorption.