Human dendritic cell subsets and function in health and disease

Abstract

The method of choice for the development of new vaccines is to target distinct dendritic cell subsets with antigen in vivo and to harness their function in situ to enhance cell-mediated immunity or induce tolerance to specific antigens. The innate functions of dendritic cells themselves may also be targeted by inhibitors or activators that would target a specific function such as interferon production, potentially important in autoimmune disease and chronic viral infections. Importantly targeting dendritic cells requires detailed knowledge of both the surface phenotype and function of each dendritic cell subset, including how they may respond to different types of vaccine adjuvants, their ability to produce soluble mediators and to process and present antigens and induce priming of naïve T cells. This review summarizes our knowledge of the functional attributes of the human dendritic cell subsets in the steady state and upon activation and their roles in human disease.

Interleukin 23 in IBD Pathogenesis

“…Furthermore, human fibroblast-like synoviocytes (ex vivo and in vivo) and human colon subepithelial myofibroblasts were shown to produce IL-23p19 upon IL-1β and TNF-α all of which suggest that non-hematopoietic sources may also contribute to IL-23 production to some extent, given the right stimulation [6,7]. Different subsets of DCs exist, defined by their developmental origin, tissue location and surface markers [8,9]. Stimulation with select ligands induces IL-23 production by CD11c + conventional DCs, pDCs or ex vivo-generated BMDC (mice) to varying degrees.…”

Bone marrow mesenchymal stem cells inhibit dendritic cells differentiation and maturation by microRNA-23b

“…Dendritic cells (DCs) are a kind of antigen-presenting cells which have important function in vivo [7]. Since DCs are the initial factors of the immune response to activate naive T cells [8], they have an indispensable role in the immune response.…”

State-of-the-art of regulatory dendritic cells in cancer

“…Lin − ZBTB46 + MHC-II + CD141 + conventional DCs (or their CD8a + CD4 − murine counterparts) typically cross-present extracellular antigens to CD8 + T cells, while Lin − ZBTB46 + MHC-II + CD1c + conventional DCs (or their CD8a − counterparts in mice) express a distinct TLR pattern (Said & Weindl, 2015) and are particularly effective at inducing Th2 responses (O’Keeffe, Mok, & Radford, 2015). In cancer, however, CD11b + conventional DCs have been found to suppress CD8 + T cell function in tumor-bearing mice, among other potential mechanisms, via L-Arginine metabolism (Norian, et al, 2009).…”

“…Exhaustive studies by Amigorena and colleagues have characterized inflammatory DCs as human CD11c + CD115 + CD1c + CD1a + FcεRI + CD206 + CD172a + CD14 + CD11b + leukocytes and CD11c + MHC-II + CD11b + F4/80 + Ly6C + CD206 + CD115 + CD107b + FcεRI + CD64 + cells in mice (Segura & Amigorena, 2013, 2014). Although their precise ontogeny in inflammatory conditions remains unclear, inflammatory DCs can certainly arise from monocytes, and produce high levels of the pro-inflammatory cytokines TNF, IL-6, and IL-12 (O’Keeffe, et al, 2015). …”