@article{fdi:010092782,
  title = {{P}ortimine {A} toxin causes skin inflammation through {ZAK}  {A}-dependent {NLRP}1 inflammasome activation},
  author = {{G}orse, {L}. and {P}lessis, {L}. and {W}earne, {S}. and {P}aradis, {M}. and {P}inilla, {M}. and {C}hua, {R}. and {L}im, {S}. {S}. and {P}elluz, {E}. and {T}oh, {G}. {A}. and {M}azars, {R}. and {B}omfim, {C}. and {H}erv{\'e}, {F}. and {L}haute, {K}. and {R}{\'e}veillon, {D}. and {S}uire, {B}. and {R}avon-{K}atossky, {L}. and {B}enoist, {T}. and {F}romont, {L}. and {P}{\'e}ricat, {D}. and {M}ertens, {K}. {N}. and {D}errien, {A}. and {T}erre-{T}errillon, {A}. and {C}hom{\'e}rat, {N}. and {B}ilien, {G}. and {S}{\'e}chet, {V}. and {C}arpentier, {L}. and {F}all, {M}. and {S}onko, {A}. and {H}akim, {H}. and {S}adio, {N}. and {B}ourdeaux, {J}. and {C}ougoule, {C}. and {H}enras, {A}. {K}. and {P}erez-{O}liva, {A}. {B}. and {B}rehmer, {P}atrice and {R}oca, {F}. {J}. and {Z}hong, {F}. {L}. and {C}ommon, {J}. and {M}eunier, {E}. and {H}ess, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{I}n 2020-2021, a "mysterious illness" struck {S}enegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. {H}ere, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate {V}ulcanodinium rugosum and its associated cyclic imine toxins. {S}pecifically, we show that the toxin {P}ortimine{A}, strongly enriched in environmental samples, impedes ribosome function in human keratinocytes, which subsequently activates the stress kinases {ZAK} alpha and {P}38 and promotes the nucleation of the human {NLRP}1 inflammasome, leading to the release of {IL}-1 beta/{IL}-18 pro-inflammatory cytokines and cell death. {F}urthermore, cell-based models highlight that naturally occurring mutations in the {P}38-targeted sites of human {NLRP}1 are unable to respond to {P}ortimine{A} exposure. {F}inally, the development and use of human organotypic skins and zebrafish models of {P}ortimine{A} exposure demonstrate that the {ZAK} alpha-{NLRP}1 axis drives skin necrosis and inflammation. {O}ur results exemplify the threats to human health caused by emerging environmental toxins and identify {ZAK} alpha and {NRLP}1 as important pharmacological targets to mitigate {P}ortimine{A} toxicity.},
  keywords = {{S}kin {P}athology ; {E}nvironmental {T}oxins ; {R}ibotoxic {S}tress {R}esponse ; {NLRP}1 ; {I}nflammasome},
  booktitle = {},
  journal = {{EMBO} {M}olecular {M}edicine},
  volume = {[{E}arly access]},
  numero = {},
  pages = {[28 p.]},
  ISSN = {1757-4676},
  year = {2025},
  DOI = {10.1038/s44321-025-00197-4},
  URL = {https://www.documentation.ird.fr/hor/fdi:010092782},
}