Generation of Tolerogenic Dendritic Cells and Their Therapeutic Applications

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that bridge innate and adaptive immune responses, thereby leading to immune activation. DCs have been known to recognize pathogen-associated molecular patterns such as lipopolysaccharides (LPS) and nucleic acids via their pattern recognition receptors, which trigger signaling of their maturation and effector functions. Furthermore, DCs take up and process antigens as a form of peptide loaded on the major histocompatibility complex (MHC) and present them to T cells, which are responsible for the adaptive immune response. Conversely, DCs can also play a role in inducing immune suppression under specific circumstances. From this perspective, the role of DCs is related to tolerance rather than immunity. Immunologists refer to these special DCs as tolerogenic DCs (tolDCs). However, the definition of tolDCs is controversial, and there is limited information on their development and characteristics. In this review, we discuss the current concept of tolDCs, cutting-edge methods for generating tolDCs in vitro, and future applications of tolDCs, including clinical use.

Quercetin‐Induced miR‐369‐3p Suppresses Chronic Inflammatory Response Targeting C/EBP‐β

“…Dendritic cells (DCs) are the most potent antigen‐presenting cells and have an important role in the crosstalk between the innate and the adaptive immune response . DCs constantly supervise all body tissues in their immature form, iDCs, and the exposure of pattern recognition receptors (PRRs) like Toll‐like receptors (TLRs), or intracellular PRRs like NOD‐like receptors (NLRs) to microbe‐associated molecular patterns (MAMPs) leads to iDCs becoming mature DCs (mDCs) . mDCs possess limited endocytosis, but exceptional T cells stimulating capacity.…”

“…[1,2] DCs constantly supervise all body tissues in their immature form, iDCs, and the exposure of pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), or intracellular PRRs like NOD-like receptors (NLRs) to microbeassociated molecular patterns (MAMPs) leads to iDCs becoming mature DCs (mDCs). [3] mDCs possess limited endocytosis, but exceptional T cells stimulating capacity. This is due to the ability to present previously encountered antigens on their major histocompatibility complex (MHC) class II.…”

CD11b+Gr‐1dim Tolerogenic Dendritic Cell–Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice

“…However, little is known about the role of tolerogenic DCs in RA ‐ associated ILD. Tolerogenic DCs can be generated from bone marrow (BM) cells in vitro using granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and factors such as interleukin‐10 (IL‐10) and transforming growth factor β (TGFβ) ; however, it is not known whether tolerogenic DCs can also be differentiated from lung‐infiltrating cells.…”

Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

“…Many methods including drug interference and genetic engineering have effectively maintained DCs in an immature state. Furthermore, artificially generated tolerogenic DCs generated by genetically modifying DCs with genes encoding immunoregulatory molecules may be a promising tool for cellular therapy after solid organ transplantation …”