Dendritic Cells as Sensors, Mediators, and Regulators of Ischemic Injury

Abstract

Dendritic cells (DCs) are highly specialized, bone marrow (BM)-derived antigen-processing and -presenting cells crucial to the induction, integration and regulation of innate, and adaptive immunity. They are stimulated by damage-associated molecular patterns (DAMPS) via pattern recognition receptors to promote inflammation and initiate immune responses. In addition to residing within the parenchyma of all organs as part of the heterogeneous mononuclear phagocyte system, DCs are an abundant component of the inflammatory cell infiltrate that appears in response to ischemia reperfusion injury (IRI). They can play disparate roles in the pathogenesis of IRI since their selective depletion has been found to be protective, deleterious, or of no benefit in mouse models of IRI. In addition, administration of DC generated and manipulated ex vivo can protect organs from IRI by suppressing inflammatory cytokine production, limiting the capacity of DCs to activate NKT cells, or enhancing regulatory T cell function. Few studies however have investigated specific signal transduction mechanisms underlying DC function and how these affect IRI. Here, we address current knowledge of the role of DCs in regulation of IRI, current gaps in understanding and prospects for innovative therapeutic intervention at the biological and pharmacological levels.

Living in a Hostile World: Inflammation, New Drug Development, and Coronavirus

“…In 1973, the dendritic cell (DC) was the first APC discovered by Canadian physician Steinman and Cohn in lymph nodes and spleen (45) (Figure 1). Mature macrophages, and other tissue-resident immune cells, also have this antigen presenting capacity, though not to the extent of DCs (46)(47)(48)(49).…”

“…In the case of infection, the bridge between innate and adaptive immunity, and induction of classical immune memory in lymphocytes, begins at the tissues with the activation of resident DCs (via complement and cytokines) (36,46,47,153). In peripheral tissues, DCs: 1) capture and process antigens, 2) express lymphocyte co-stimulatory molecules, 3) migrate to secondary lymphoid organs and 3) secrete "instructive" cytokines to initiate and drive lymphocyte differentiation and clonal expansion (Figure 1) (128).…”

“…Th2 cytokines also help to maintain the presence of the M2 phenotype (155)(156)(157)(158)(159). In addition, DCs induce the production of T regulatory cells that suppress the destructive pro-inflammatory activities of Th1 cells by secreting cytokines, such as TGF-b1, IL-10 and IL-35, and enhance M2 responses to promote cell clearance (47,160,162,163). Collectively, these changes limit inflammation and create a permissive healing environment (Figure 3).…”

Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis

“…Conventional DCs exert a key function ranging from pathogen detection to cancer immunity as they are critical, through antigen presentation, to initiate specific T-cell responses. On the other, pDCs display high anti-viral activities due to their ability to produce type I interferon and are thought to be involved in immune tolerance (39,40).…”

Dendritic Cells: Versatile Players in Renal Transplantation

“…The interaction between DCs and T lymphocytes triggers a socalled acute rejection through the conventional pathway-donor DCs present alloantigen to recipient T cells directly (82, 83) (Figure 2). At first, the ischemia-reperfusion condition drives donor DCs to induce acute rejection (14). Secondly, active DCs search for immature or memory T cells attracted by the chemical FIGURE 2 | Immature DCs can be activated by antigens derived from ischemia-reperfusion and act as the role of powerful antigen-presenting cells to trigger antibody-mediated rejection and cell-mediated rejection.…”