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- Title
CD8<sup>+</sup> lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury.
- Authors
Chakraborty, Rituparna; Chandra, Janin; Cui, Shuai; Tolley, Lynn; Cooper, Matthew A.; Kendall, Mark; Frazer, Ian H.
- 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 ( DAMPs), as opposed to pathogen-associated molecules ( PAMPs), 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 CD8+ T-cell responses, and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox- CD11cCre+ mice, we demonstrate that CD8+ lineage DCs are required to induce OVA-specific CD8+ T-cell responses following heat injury. Consistent with this observation, intradermal administration of CD8+ lineage DCs but not CD11b+ lineage DCs restores priming of CD8+ T-cell responses in Casp-1−/− mice. Thus, we conclude that a sterile injury induces CD8+ T-cell immune responses to local antigen through caspase-1 activation and requires CD8+ lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.
- Subjects
CD8 antigen; DENDRITIC cells; PATHOGENIC microorganisms; PHYSIOLOGICAL effects of cytokines; SKIN disease immunology; AUTOIMMUNITY
- Publication
Experimental Dermatology, 2018, Vol 27, Issue 1, p71
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.13436