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As sentinels of the immune system, dendritic cells (DCs) are located in all tissues, especially those at the interface between the external environment and the body, such as lung, intestine, and skin. DCs are divided into plasmacytoid DCs (pDCs) and conventional DCs (cDCs), cDCs are further split into type 1 (cDC1) and type 2 (cDC2). Functionally, cDCs include two states: immature and mature. Immature DCs are professional in uptaking and processing antigens, and mature DCs are specialist in antigen presentation. It has been observed that immature cDCs can induce immune tolerance, while mature cDCs induce Th2 or Th1 immune responses.
Table 1. Major human DC subsets.
|DC subsets||Phenotype||Key features|
|Plasmacytoid DC||Lineage− CD14− CD11c−||Produce type 1 IFNs in response to viral pathogens;|
Express high TLR7 and TLR9
|CD123+ BDCA-2 (CD303)+ BDCA-4 (Nrp)+|
|Myeloid cDC1||Lineage− CD11c+||T cell priming and activation;|
|MHC II+ CD86+|
|Myeloid cDC2||Lineage− CD11c+||Cross-presentation of exogenous Ags to CD8 T cells;|
Express high TLR3 and TLR8
|MHC II+ CD86+|
|BDCA-3 (CD141)+ CLEC9A+ XCR1+|
DC Linking Innate and Adaptive Immunity
DCs play a vital role in the immune system and effectively link innate and adaptive immune responses. DCs are derived from progenitor cells in the bone marrow and reside in peripheral tissues in an immature state. Immature DCs (iDCs) have been shown to induce peripheral tolerance by causing T cell anergy, directing T cell deletion or by inducing the generation of regulatory T cells (Treg). Under appropriate stimulation mediated by inflammation and pathogen, iDCs undergo maturation. Mature DCs express costimulatory molecules, secrete cytokines, and migrate to lymphoid organs where they activate antigen-specific T cells.
Exploiting the immunomodulatory capabilities of DCs holds broad prospects in treating cancer, autoimmune diseases, and preventing transplant rejection. DCs can be the most effective adjuvant to enhance the host's immune defenses. In the case of cancer, tumors have been shown to inhibit DCs by secreting anti-inflammatory cytokines such as IL-10, thereby regulating local DCs to form inhibitory T cells. To subvert these mechanisms, DCs can be generated ex vivo and loaded with tumor antigens, and then re-injected to enhance the host's immunity to tumor cells. DC vaccines generated in this way are generally safe with minimal side effects, and have proven to be feasible and effective for certain patients.