Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells

Circulating heat shock protein (HSP)-27 is associated with tumor progression and increased post-injury infection. Extracellular HSP-27 might alter monocyte (MO)derived DC and/or M(D function to mediate immunosuppression. HSP-27 treatment inhibited expression of CD1a and CD1b/c, antigen uptake, and allogeneic T cell induction (MLR) by IL-4 + GM-CSF-differentiated human DC while increasing some M Phi) characteristics (up arrow CD14, up arrow CD16, up arrow CD163). MO cytokine receptor profiles elicited by 24-h exogenous HSP-27 treatment remained supportive of immature DC (iDC) emergence (up arrow IL-4R, down arrow IL-6R, down arrow M-CSFR). IL-10, IL-6, and M-CSF (which promote M(D differentiation) were significantly increased in IL-4 + GM-CSF + HSP-27 MO -> iDC differentiation cultures. However, HSP-27 treatment during MO differentiation to DC increased programmed cell death ligand I coinhibitor and depressed CD86 costimulator expression in parallel to decreased iDC MLR activity. This suggested that increased M(D differentiation was not solely responsible for HSP-27 reduction of differentiating DC activity. HSP-27 treatment actually depressed the phagocytic capacity of MO differentiated to M(D by IL-10 or M-CSF culture. CD163 (hemoglobin receptor) expression was depressed on M-CSF + HSP-27 MO-derived M(D. HSP-27-mediated inhibition of MO -> iDC differentiation was reversed by p38 alpha & beta inhibitor. (SB202190) addition or TLR4 receptor modulation. HSP-27 impaired appropriate MO -> iDC and MO -> M Phi differentiation modulating expression of receptors necessary for their proper functions. This suggests that endogenous HSP-27 has immunoregulatory activities which could contribute to immunopathology.