Abstract
Dendritic cells (DCs) are well-established as major players in the regulation of immune responses. They either induce inflammatory or tolerogenic responses, depending on the DC-subtype and stimuli they receive from the local environment. This dual capacity of DCs has raised therapeutic interest for their use to modify immune-activation via the generation of tolerogenic DCs (tolDCs). Several compounds such as vitamin D3, retinoic acid, dexamethasone, or IL-10 and TGF-β have shown potency in the induction of tolDCs. However, an increasing interest exists in defining tolerance inducing receptors on DCs for new targeting strategies aimed to develop tolerance inducing immunotherapies, on which we focus particular in this review. Ligation of specific cell surface molecules on DCs can result in antigen presentation to T cells in the presence of inhibitory costimulatory molecules and tolerogenic cytokines, giving rise to regulatory T cells. The combination of factors such as antigen structure and conformation, delivery method, and receptor specificity is of paramount importance. During the last decades, research provided many tools that can specifically target various receptors on DCs to induce a tolerogenic phenotype. Based on advances in the knowledge of pathogen recognition receptor expression profiles in human DC subsets, the most promising cell surface receptors that are currently being explored as possible targets for the induction of tolerance in DCs will be discussed. We also review the different strategies that are being tested to target DC receptors such as antigen-carbohydrate conjugates, antibody-antigen fusion proteins and antigen-adjuvant conjugates.
Highlights
Dendritic cells (DCs) are important antigen presenting cells during the induction of immune responses and are essential in directing immune responses toward either immunity or tolerance
There has been an increasing interest in moving toward in vivo targeting strategies where the induction of tolerance is achieved by targeting different receptors on DCs in their natural environment with antigendelivering antibodies and antigen-carbohydrate conjugates
The potential for future clinical translation and therapeutic application of in vivo antigen targeting to DCs is very promising, additional research is necessary to decipher the specific molecular mechanisms involved in the anti-disease tolerance promoted by such DCs
Summary
Dendritic cells (DCs) are important antigen presenting cells during the induction of immune responses and are essential in directing immune responses toward either immunity or tolerance. This decision is of great importance as undesired inflammatory responses could cause autoimmune or allergic diseases. DCs capture antigens and process them while migrating to the draining lymph nodes, where they present antigen-specific peptides to T lymphocytes. This migration process causes a dramatic transformation of the DC phenotype, called maturation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
