RNA sequencing of chronic GVHD skin lesions defines shared and unique inflammatory pathways characterizing lichen planus and morphea
Habib Zouali, Juliette Lemasson, Andreea Calugareanu, Christophe Battail, David Michonneau, Hélène le Buanec, Chloé Grolleau, Charles Cassius, Marie Robin, Marine Merandet, Gabor Dobos, Thibault Mahevas, Michel Rybojad, Adèle de Masson, Reyhan Amode, Anne Boland, Laurence Michel, Flore Sicre de Fontbrune, Régis Peffault de Latour, Patrick Bruneval, Hafid Ait-Oufella, Maxime Battistella, Marie Jachiet, Martine Bagot, Jean-François Deleuze, Gérard Socié, Jean-David Bouaziz
Abstract
Cutaneous involvement of chronic graft-versus-host disease (cGVHD) has a wide range of manifestations including a lichenoid form with a currently assumed mixed Th1/Th17 signature and a sclerotic form with Th1 signature. Despite substantial heterogeneity of innate and adaptive immune cells recruited to the skin and of the different clinical manifestations, treatment depends mainly on the severity of the skin involvement and relies on systemic, high-dose glucocorticoids alone or in combination with a calcineurin inhibitor. We performed the first study using RNA sequencing to profile and compare the transcriptome of lichen planus cGVHD (n = 8), morphea cGVHD (n = 5), and healthy controls (n = 6). Our findings revealed shared and unique inflammatory pathways to each cGVHD subtype that are both pathogenic and targetable. In particular, the deregulation of IFN signaling pathway was strongly associated with cutaneous cGVHD, whereas the triggering receptor expressed on myeloid cells 1 pathway was found to be specific of lichen planus and likely contributes to its pathogenesis. The results were confirmed at a protein level by performing immunohistochemistry staining and at a transcriptomic level using real-time quantitative polymerase chain reaction.