Local Immune Modulation of Macrophages and Dendritic Cells

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Background

Dendritic cells as well as macrophages are the guardians of the immune system in the tissue and are well known as central mediators of immune responses. Their activity depends highly on the micro-environmental stimuli.

Conventional Dendritic cells (DC) are adult hematopoietic-derived mononuclear phagocytes with a central role for priming naive T cells. This process is carried out by sensing danger signals through pattern recognition receptors (PRRs) and processing foreign epitopes like viruses, bacteria, or foreign tissue such as in solid organs or tissue grafts. During this process, DC phenotypically mature with upregulation of MHC and costimulatory molecules so that they can efficiently prime T cells to fight infections and induce inflammation. In so doing, DC can also be modulated by various factors during pathological conditions. For example, it has been shown that VEGF secreted by tumor cells influence the differentiation of DC. Moreover, hypoxia, accumulation of adenosine, increased levels of lactate, and decreased pH are shown to impair the normal function of DCs. Various additional factors like sCD83, ALCAM, and even the VEGF blocking therapies have also been shown to modulate the activation status of DC.

Macrophages are perhaps the most functionally diverse cells of the mononuclear phagocyte system. They are derived from prenatal cells that become tissue-residents, or alternatively from adult hematopoietic derived monocytes. Their activities play important roles in tissue development, homeostasis, repair, and immunity. “Classical” activated macrophages (CAM) occur via stimulation by proinflammatory mediators, such as IFN-γ, TNF-α, or LPS, occurring primarily in early phases of the inflammatory response with an increased expression of proinflammatory cytokines, antigen presentation, and production of nitrogen and oxygen radicals. In contrast, “alternative” activated macrophages (AAM) may be mediated by a number of immunomodulatory and immunosuppressive factors, including IL-4 and IL-13, showing increased activity in signaling pathways, which are important for the termination of an immune response.

Local immune modulation has become increasingly more attractive for the treatment of different diseases like cancer, chronic inflammation, or autoimmune diseases as well as in transplant immunology, where a locally restricted treatment of the graft or the host is possible. In this Research Topic, we welcome the submission of Original Research, Reviews, Clinical Trials, focusing on, but not limited to, the following subtopics:

1. Immunological processes involving dendritic cells and macrophages in the microenvironment of the graft-host interface as well as the sides of chronic inflammation and lesions caused by autoimmune diseases.
2. New strategies to generate locally tolerogenic dendritic cells and AAMs to either induce graft tolerance or to break the vicious cycle of chronic inflammation or autoimmune diseases.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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