177 Chronic graft-versus-host disease exhibits distinct Th1-skewing and barrier abnormalities in the skin

Chronic graft-versus-host disease (GvHD) is a common T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation that frequently manifests in the skin. Prior studies have delineated complex interplay Th1/Th2 donor T-cell polarization; however, understanding molecular mechanisms underlying cutaneous GvHD remains limited. In this RNA-seq study, we characterize transcriptome skin biopsies from 10 patients with GvHD, 12 atopic dermatitis/AD (paired lesional/LS and nonlesional/NL), healthy controls. Differentially expressed genes (DEGs) were defined as |fold-change|>2 false discovery rate<0.05. We found strong significant Th1 polarization (e.g. CXCL9/10/11, IFN-γ) relative to both controls AD LS NL. Significant Th2-skewing IL-4R, IL-10/13, CCL7) was strongest controls, some overlap which differentially upregulated IL-10, CCL5/7, OX40L but downregulated CCL17/22. Compared also shared barrier abnormalities KRT89, CDH12 [down]; SPRR2G [up]), notable differences. many epidermal hyperplasia DEGs S100s, SPRR1A/B) lipid metabolism FABP7, ELOVL3, FADS2), while more modest modulation observed demonstrated enrichment several markers CDH11, LIPA, APOL1) not seen AD. Gene set variation analysis reflected marker-level findings additionally showed upregulation IL-12/23-related multiple cytokine IFN-γ, IL-4)-mediated fibroblast- keratinocyte-associated pathways. These data suggest chronic, are characterized by differential Th1/Th2/Th17 distinct signatures, providing comparative insight into profiles these inflammatory diseases.