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. We performed the first study using RNA-Seq to profile and compare the transcriptome of lichen planus cGVHD (LP, n=8), morphea cGVHD (n=5), and healthy controls (CONT, n=6). We identified 2945 DEG when comparing LP to CONT, and 1652 when comparing morphea to CONT. 979 DEG were shared between the 2 subtypes (e.g., CXCL9, CXCL10, CXCL11). GSEA identified 2 gene sets enriched in both subtypes that are related to IFNγ and α responses. Using IPA we identified “IFN signaling” as the most important canonical pathway predicted to be activated. 208 DEGs were identified when comparing LP to morphea. Among the most significant canonical pathways, triggering receptor expressed on myeloid cells 1(TREM1) signaling pathway was predicted to be activated. TREM-1 is a cell surface receptor mainly expressed on myeloid cells, known to amplify an inflammatory response. In conclusion, we unravelled common and unique inflammatory pathways in cGVHD, including IFN signaling pathway that seems to play an important role in both lichen planus and morphea cGVHD, as well as the TREM1 signaling pathway that could be a promising therapeutic target in LP cGVHD.

ESDR023 - RNA sequencing of chronic GVHD skin lesions identifies TREM1 as a possible therapeutic traget in lichen planus

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING