The Role of Plasmacytoid Dendritic Cells in Gut Health

Abstract

Plasmacytoid dendritic cells (pDCs) are a unique subset of cells with different functional characteristics compared to classical dendritic cells. The pDCs are critical for the production of type I IFN in response to microbial and self-nucleic acids. They have an important role for host defense against viral pathogen infections. In addition, pDCs have been well studied as a critical player for breaking tolerance to self-nucleic acids that induce autoimmune disorders such as systemic lupus erythematosus. However, pDCs have an immunoregulatory role in inducing the immune tolerance by generating Tregs and various regulatory mechanisms in mucosal tissues. Here, we summarize the recent studies of pDCs that focused on the functional characteristics of gut pDCs, including interactions with other immune cells in the gut. Furthermore, the dynamic role of gut pDCs will be investigated with respect to disease status including gut infection, inflammatory bowel disease, and cancers.

Toll Like Receptor 9 Pathway Mediates Schlafen+-MDSC Polarization During Helicobacter-Induced Gastric Metaplasias

“…During an infection, DCs migrate to the epithelial layer and intercalate into the epithelium to sample the H. pylori-colonized lumen 28 . Here we report that after 2 months of a Helicobacter infection, IFNα was expressed by both epithelial cells and infiltrating immune cells within the lamina propria, many of which were pDCs 12,29 . Once activated, pDCs secrete copious amounts of type I IFNs via TLR9-MyD88-IRF7 inflammasome signaling 29,30 .…”

“…Here we report that after 2 months of a Helicobacter infection, IFNα was expressed by both epithelial cells and infiltrating immune cells within the lamina propria, many of which were pDCs 12,29 . Once activated, pDCs secrete copious amounts of type I IFNs via TLR9-MyD88-IRF7 inflammasome signaling 29,30 . TLR9 activation by H. pylori immunomodulatory DNA sequences can enhance H. pylori chronicity by suppressing pro-inflammatory cells 11,14,28. In addition, the CpG-DNA-binding protein high-mobility group box 1 (HMGB1)…”

Functions of Dendritic Cells and Its Association with Intestinal Diseases

“…pDCs are mainly developed from IL-7R + lymphoid progenitor cells with the assistance of transcription factors E2-2 and IRF8 [ 19 , 33 ]. pDCs selectively express TLR2, TLR7, TLR9, TLR11, amd TLR12, and it is endosomal sensors TLR7 and TLR9 that mainly mediate the recognition of microbial pathogens [ 34 ].…”

Host Protective Immune Responses against Influenza A Virus Infection

“…pDCs, which are primarily known as producers of type I IFNs [138], seem to play a minor role in the defense against influenza virus infection. Despite the accumulation of pDCs in the lung following influenza virus infection, pDC-depleted mice showed identical survival rate and body weight loss compared to healthy controls [121,139].…”