Fig. 4

Mechanisms underlying dendritic cells response to biomaterials. a The mechanism of integrins. β2 integrins are virtually the first receptors adhering to the ECM proteins, thus initiating NF-kB signaling pathways, which potentiates multiple inflammatory events. b The mechanism of TLRs, especially of TLR 2/4/6. TLR 2/4/6 signals through MyD88 or TRIF respectively, which terminated at two events: (i) activates the NF-kB-mediated regulation of inflammatory (like TNF-α or IL-6) and immunoregulatory genes (like TGF-β or IL-10); (ii) phosphorylates IRF3 and IRF7, leading to the consequential expression of co-stimulatory molecules such as CD80 and CD86 and production of type I interferons (e.g., IFN-α and IFN-β). c The mechanism of CLRs. DC-SIGN and CD205 are among the most efficient CLRs that enhance antigen uptake and presentation by DCs. d The mechanism of inflammasomes, especially of NLRP3. In the presence of NF-kB, cytosolic NLRP3 can also be stimulated via biomaterial-derived signals and forms an intracellular multiprotein complex that catalyzes the conversion of caspase-1, thus regulating the production of highly inflammatory cytokines such as IL-1β and IL-18. e The mechanism of autophagy. DCs in the presence of certain biomaterials express high levels of ILT3 and PDL1, as characteristic co-inhibitory molecules of tolDC, while upregulate transcriptional profile of ATGs such as ATF4 and FOXO3