Fig. 7.

Plasticity of MSCs in immunoregulation: the crosstalk between microenvironments and MSCs. The immunomodulatory function of MSCs relies on the kinds and concentrations of microenvironment components. As a DAMP, HMGB1 plays an important role in initiating and exacerbating immune responses in local environment in response to damages. A subsequent robust pro-inflammatory response renders MSCs immunosuppressive. HMGB1 itself, however, directly reversed the immunosuppression of MSCs through at least in part inhibiting iNOS expression involving TLR4 pathways. Because the treatment efficacy of MSCs is dependent on the immunosuppression to a great extent, HMGB1 can further modulate the reparative effect of MSCs via an integrated action in the microenvironments