Targeting interrelated NLRP3 and NF-κβ signaling pathways to develop enhanced tolerogenic dendritic cells: Promising...

Proper immune response needs a regulated interaction between adaptive and innate immunity and dendritic cells (DCs) as professional antigen presenting cells coordinate their interaction. In order to maintain the balance between tolerance and initiation of immune response, these DCs should be activated in a regulated manner which is managed by diverse signaling pathways including nuclear factor kappa light chain enhancer of activated B cells (NF-κβ) and NLR family pyrin domain containing 3 (NLRP3). According to the vital role of DCs in immunity, it is a promising strategy to induce tolerogenic DCs (TolDCs) to suppress autologous T cell responses in patients with autoimmune disorders and targeting inflammatory signaling pathways is a potent strategy for induction of mentioned TolDCs. NF-κβ and NLRP3 signaling pathways play significant role in maturation, antigen presentation, and inflammatory function of DCs and finally affect their immune response which subsequently contributes to differentiation of T cells. According to the stated vital role of signaling pathways in DCs and their involvement in progression of autoimmune disorders, in this study we will review NF-κβ and NLRP3 signaling pathways and their contribution to DCs' immunogenicity and functionality and it will be discussed that how these signaling pathways are strictly regulated. Furthermore, this review sheds light on therapeutic role of NF-κβ and NLRP3 targeting for induction of potent TolDCs for the benefit of patients with diverse autoimmune disorders. Finally, due to the well-known role of NF-κβ as primary needed signal for assembly and full function of NLRP3 inflammasome we will mention the cross-talk between NF-κβ and NLRP3 pathways and highlight their interrelated targeting as a mechanistically rational approach that warrants future experimental investigation to evaluate effects of their simultaneous modulation for induction of favorable TolDC vaccines with both NF-κβ and NLRP3 being suppressed that not only disrupts the immunogenic function of DCs by inhibition of NF-κβ, but also prevents full activation of NLRP3 inflammasome.