Abstract
Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialised in secreting high levels of type I interferons. pDCs play a crucial role in antiviral immunity and have been implicated in the initiation and development of many autoimmune and inflammatory diseases. This review summarises the latest advances in recent years in several aspects of pDC biology, with special focus on pDC heterogeneity, pDC development via the lymphoid pathway, and newly identified proteins/pathways involved in pDC trafficking, nucleic acid sensing and interferon production. Finally, we also highlight the current understanding of pDC involvement in autoimmunity and alloreactivity, and opportunities for pDC‐targeting therapies in these diseases. These new insights have contributed to answers to several fundamental questions remaining in pDC biology and may pave the way to successful pDC‐targeting therapy in the future.
Highlights
Human plasmacytoid dendritic cells were initially described 20 years ago by the Liu and Colonna groups.[1,2] pDCs are continuously generated from haematopoietic stem cells in the bone marrow (BM) via both myeloid and lymphoid precursors
This review summarises the recent advances in pDC biology, including pDC heterogeneity, lymphoid pathway of pDC development and novel nucleic acid sensing patterns during IFN-I production
Phase III: response at week 52: anifrolumab (47.8%) vs placebo (37.5%) Phase II ongoing Phase II ongoing Phase II met primary endpoint Primary endpoint not met in Phase II, but disease improved in patients with low ISM scores IFN-a kinoid was well tolerated in Phase I; Phase II ongoing Ongoing BIIB059 ameliorated skin lesion in Phase I; Phase II ongoing
Summary
Human plasmacytoid dendritic cells (pDCs) were initially described 20 years ago by the Liu and Colonna groups.[1,2] pDCs are continuously generated from haematopoietic stem cells in the bone marrow (BM) via both myeloid and lymphoid precursors. Plasmacytoid dendritic cells produce another class of potent innate antiviral interferons, the IFN-ks or type III IFNs (IFN-III) in response to viruses or synthetic TLR ligands.[81] The IFN-ks mainly serve as a first line of defence at the mucosal barrier, given that the IFN-k receptor (IFN-kR), the specific receptor for IFN-k, is restrictively expressed on cells of epithelial lineage and on certain human leucocytes including pDCs and B cells.[82] Importantly, IFN-ks are observed to provide non-redundant antiviral protection at mucosal sites including the respiratory and gastrointestinal tract.[83,84] Recently, IFN-ks have found to be involved in autoimmunity and antitumor immunity.[85,86] Besides, IFN-ks could positively regulate pDC functions, including interferon-dependent gene transcription,[87] production of cytokines (including IFN-I),[88] maturation[81] and survival.[88] during virus infection, the local defence by IFN-ks at mucosal sites may enhance the subsequent systematic IFN-I responses. Mobilisation of colitogenic phagocytes into the inflamed colon N/A
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