Title:Inflammasome in Dendritic Cells Immunobiology: Implications to Diseases and Therapeutic Strategies
Volume: 18
Issue: 9
关键词:
佐剂，树突状细胞，炎性体，NLR，TLR，NLRP3，DAMPs
摘要: Background: An intricate interplay between innate and adaptive immune cells is crucial for
an effective immune response during disease, infection and vaccination. This interplay is mainly performed
by dendritic cells (DCs), which are professional antigen presenting cells with unparalleled capacity
to translate innate to adaptive immunity. They effectively recognize and uptake antigens, migrate to
lymphoid tissues, and activate naïve T-cells. Indeed, DCs have numerous germline encoded pattern recognition
receptors (PRR) that recognize conserved pathogen associated molecular patterns (PAMPs) or
danger associated molecular patterns (DAMPs). While some PRRs like Toll-like receptors (TLRs) recognize
PAMPs and DAMPs at the cell surface and in endosomal/lysosomal compartments, others, such
as NOD-like receptors (NLRs), act as cytosolic sensors. NLRs activation through recognition of PAMPs
and DAMPs leads to the assembly of signaling multimeric protein complexes named inflammasomes.
Inflammasomes are important regulators of caspase 1, the enzyme responsible for the proteolytically
cleavage of precursors’ pro-IL-1β and pro-IL-18 into their active form.
Objective: To unveil how inflammasomes are related to maturation, migration, antigen presenting
function and DCs ability to fine tune adaptive immune responses.
Conclusion: Several studies show that in danger/infectious scenarios NLR and TLR synergize to expand
DCs maturation, migration, antigen presenting function and adaptive immune system activation. However,
in the absence of a danger scenario, and without TLR engagement, inflammasome activation stimulates an
immunosuppressive profile on DCs. Overall, it is clear from literature that activation of the inflammasome
in DCs should not be viewed in isolation but rather considering its interconnections with the various PPRdriven
pathways. Due to the increasing evidences of inflammasome involvement in multiple inflammatory
and immune diseases, this information is of utmost importance since precise inflammasome pharmacological
targeting could lead to considerable clinical utility through fine-tuned targeted therapies.
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