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CD 8 + lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury
Author(s) -
Chakraborty Rituparna,
Chandra Janin,
Cui Shuai,
Tolley Lynn,
Cooper Matthew A.,
Kendall Mark,
Frazer Ian H.
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13436
Subject(s) - inflammasome , immune system , dendritic cell , acquired immune system , immunology , chemistry , microbiology and biotechnology , biology , inflammation
Abstract The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage‐associated molecular patterns ( DAMP s), as opposed to pathogen‐associated molecules ( PAMP s), regulate the immune response to non–self‐antigens presented at the site of a physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterized by local cell death and caspase‐1 activation without demonstrably disrupting skin integrity. Co‐delivery of ovalbumin ( OVA ) with heat injury induces OVA ‐specific CD 8 + T‐cell responses, and this is dependent on caspase‐1 activation and MyD88 signalling. Using Id2flox/flox‐ CD 11cCre+ mice, we demonstrate that CD 8 + lineage DC s are required to induce OVA ‐specific CD 8 + T‐cell responses following heat injury. Consistent with this observation, intradermal administration of CD 8 + lineage DC s but not CD 11b + lineage DC s restores priming of CD 8 + T‐cell responses in Casp‐1 −/− mice. Thus, we conclude that a sterile injury induces CD 8 + T‐cell immune responses to local antigen through caspase‐1 activation and requires CD 8 + lineage DC s, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.