The inflammatory properties of HMGB1 depend on the ability to complex with soluble moieties, including nucleic acids, microbial products (LPS), cytokines (IL-1b) and chemokines. Campana et al. 44 reported that HMGB1 secretion is required for CXCL12 (SDF-1)-dependent migration of DCs. In addition, HMGB1 protects the conformation of CXCL12 in a reducing environment, a state existing in the draining lymph node. However, only a partial inhibition of DC migration was observed in the presence of a CXCL12 inhibitor or HMGB1 A box, suggesting that multiple receptors are responsible for mediating the DC response to the HMGB1/ CXCL12 complex. An interesting study performed in CD24deficient mice revealed how the host distinguishes between danger versus pathogen PAMPs. 45 The proinflammatory activity of HMGB1 is regulated by CD24, which associates with HMGB1, thus inhibiting NF-kappa B activation occurring through CD24 association with Siglec-10. Thus, this CD24-Siglec-10 pathway protects the host against a lethal response to pathological cell death, but it would allow an appropriate response to invading pathogens. 45 