CD8+T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production

Deregulated cd8+ t cell cytotoxicity plays a central role in enhancing disease severity in several conditions. however,we have little understanding of the mechanisms by which immunopathology develops as a consequence of cytotoxicity. using murine models of inflammation induced by the protozoan parasite leishmania,and data obtained from patients with cutaneous leishmaniasis,we uncovered a previously unrecognized role for nlrp3 inflammasome activation and il-1β release as a detrimental consequence of cd8+ t cell-mediated cytotoxicity,ultimately resulting in chronic inflammation. critically,pharmacological blockade of nlrp3 or il-1β significantly ameliorated the cd8+ t cell-driven immunopathology in leishmania-infected mice. confirming the relevance of these findings to human leishmaniasis,blockade of the nlrp3 inflammasome in skin biopsies from leishmania-infected patients prevented il-1β release. thus,these studies link cd8+ t cell cytotoxicity with inflammasome activation and reveal novel avenues of treatment for cutaneous leishmaniasis,as well as other of diseases where cd8+ t cell-mediated cytotoxicity induces pathology. © 2017 novais et al.