Microbiota and caspase-1/caspase-8 regulate IL-1β-mediated bone disease

A leucine-to-proline missense mutation at residue 98 in the proline-serine-threonine phosphatase interacting protein 2 (Pstpip2) gene leads to autoinflammatory disease that is characterized by splenomegaly, necrosis, and spontaneous development of osteomyelitis in mice (Pstpip2^cmo). Disease progression in these mice resembles that of chronic recurrent multifocal osteomyelitis in humans. Our group and others have shown that disease progression in Pstpip2^cmo mice is mediated by the cytokine IL-1β, independently of inflammasomes or IL-1α. Our recent publication highlighted herein establishes that diet-induced changes in intestinal microbiota provide protection against the development of osteomyelitis in Pstpip2^cmo mice. Moreover, the proteases caspase-1 and caspase-8 have redundant roles in cleaving IL-1β and promoting disease. This addendum reviews the current literature on the Pstpip2^cmo murine disease model and the clinical significance of the role of PSTPIP2 in regulating autoinflammatory osteomyelitis, which is mediated by innate components of immune cells.