Journal
EXPERIMENTAL DERMATOLOGY
Volume 27, Issue 1, Pages 71-79Publisher
WILEY
DOI: 10.1111/exd.13436
Keywords
Caspase-1; heat injury; MyD88 signalling; OVA-specific CD8(+) T-cell responses; toll-like receptor
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Funding
- National Health and Medical Research Council of Australia
- Australian Cancer Research Foundation
- Australian Research Council
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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.
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