Various
subtypes of immunocytes react against implanted biomaterials
to eliminate the foreign body object from the host’s body.
Among these cells, dendritic cells (DCs) play a key role in early
immune response, later engaging lymphocytes through antigens presentation.
Due to their capability to induce tolerogenic or immunogenic
responses, DCs have been considered as key therapeutic targets for
immunomodulatory products. For instance, tolerogenic DCs are
applied in the treatment of autoimmune diseases, rejection of allograft
transplantation, and implanted biomaterial. Due to the emerging importance
of DCs in immunomodulatory biomaterials, this Review summarizes
DCs’ responsessuch as adhesion, migration, and maturationto
biomaterials. We also review some examples of key molecules and their
applications in DCs’ immunoengineering. These evaluations
would pave the way for designing advanced biomaterials and nanomaterials
to modulate the immune system, applicable in tissue engineering, transplantation,
and drug delivery technologies.
Dendritic cells (DCs), in response to the biomaterials, utilize toll‐like receptors (TLRs) to become mature or tolerogenic through TLRs‐dependent signaling pathways, especially TLR4. Regarding the physicochemical properties of biomaterials, some of such signaling pathways are activated. Unsaturated fatty acids have been explored as an antagonist for TLRs and lead to the tolerogenic phenotype of DCs. Here we showed that, although cultured DCs on both chitosan and Alginate‐polyethyleneimine (Alg‐PEI) films became fully mature, 10‐hydroxy‐2‐decanoic acid (10‐HDA), an unsaturated fatty acid found in royal jelly, led to the tolerogenic immunophenotype of DCs on both films. The cultured cells on the films possessed iDCs‐like morphology in the presence of 10‐HDA. Moreover, 10‐HDA expressed lower levels of CD80, CD83, CD86, and HLA‐DR, a higher level of IL‐10, and lower level of IL‐12 in the cultured DCs on both films. Furthermore, HEK293T cells expressing only TLR4 (HEK‐TLR4 cells) were co‐cultured with LPS, a specific agonist for TLR4, and 10‐HDA. The 10‐HDA significantly reduced the expression of tumor necrosis factor‐a (TNF‐α) in the HEK‐TLR4 cells compared to treated only with LPS. These findings indicate that the 10‐HDA acts as an antagonist of TLR4; therefore, potentially can be used in autoimmune diseases and preventing the rejection of biomaterials implantation and allograft transplantation.
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