Cytosolic RNA:DNA Duplexes Generated by Endogenous Reverse Transcriptase Activity as Autonomous Inducers of Skin Inflammation in Psoriasis

Jean-Pierre Molès (1) , Anthony Griez (1) , Jean-Jacques Guilhou (2, 3) , Céline Girard (1, 3) , Nicolas Nagot (1, 3) , Philippe van de Perre (1, 3) , Pierre Dujols (1, 3)

1 Pathogénèse et contrôle des infections chroniques (PCCI)
2 UM - Université de Montpellier
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

Psoriasis is a chronic skin disease of unknown ætiology. Recent studies suggested that a large amount of cytosolic DNA (cyDNA) in keratinocytes is breaking keratinocytes DNA tolerance and promotes self-sustained inflammation in the psoriatic lesion. We investigated the origin of this cyDNA. We show that, amongst all the possible DNA structures, the cyDNA could be present as RNA:DNA duplexes in keratinocytes. We further show that endogenous reverse transcriptase activities generate such duplexes and consequently activate the production of Th1-inflammatory cytokines. These observations open a new research avenue related to endogenous retroelements for the aetiology of psoriasis and probably of other human chronic inflammatory diseases.

Domaines: Médecine humaine et pathologie

Jean-Pierre Molès, Anthony Griez, Jean-Jacques Guilhou, Céline Girard, Nicolas Nagot, et al.. Cytosolic RNA:DNA Duplexes Generated by Endogenous Reverse Transcriptase Activity as Autonomous Inducers of Skin Inflammation in Psoriasis. PLoS ONE, 2017, 12 (1), pp.e0169879. ⟨10.1371/journal.pone.0169879⟩. ⟨hal-01792425⟩