Development of personalized treatment regimens is hampered by lack of insight into how individual animal models reflect subsets of @entity1 disease, and autoimmune and inflammatory conditions have proven resistant to such efforts. @entity2631 is a lethal @entity792 characterized by @entity82 , with no effective therapy. Comparative gene expression profiling showed that @entity19 @entity2132 ( @entity2132 ) approximates an inflammatory subset of @entity2631 estimated at 17% to 36% of @entity1 analyzed with diffuse, 28% with limited, and 100% with @entity2631 . Both @entity2132 and the inflammatory subset demonstrated @entity4047 cytokine pathway activation. Host dermal myeloid cells and graft T cells were identified as sources of @entity4047 in the model, and @entity74 of either @entity4047 or @entity9597 , an @entity4047 signal transducer, protected the host from disease. To identify therapeutic targets, we explored the intersection of genes coordinately up-regulated in @entity2132 , the @entity1 inflammatory subset, and @entity4047 -treated fibroblasts; we identified chemokine @entity2842 as a potential target. Treatment with anti- @entity2842 antibodies prevented @entity2132 . Last, we showed that @entity4047 pathway activation in @entity2631 @entity1 correlated with clinical skin scores, a marker of disease severity. Thus, an inflammatory subset of @entity2631 is driven by @entity4047 and may benefit from @entity4047 or @entity2842 blockade. This approach serves as a model for personalized translational medicine, in which well-characterized animal models are matched to molecularly stratified @entity1 subsets.

Interspecies comparison of @entity1 and @entity19 XXXX reveals IL-13 and CCL2 as disease subset-specific targets.

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity9597 :: ('3566', 'Gene') :: ['IL-4Ra'] @entity4047 :: ('3596', 'Gene') :: ['IL-13'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity2631 :: ('MESH:D012594', 'Disease') :: ['Scleroderma', 'localized scleroderma', 'scleroderma'] @entity2842 :: ('6347', 'Gene') :: ['CCL2'] @entity2132 :: ('MESH:D006086', 'Disease') :: ['sclerodermatous graft-versus-host disease', 'sclGVHD'] @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic deficiency'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease']
@entity2631 :: (MESH:D012594,Disease) :: ['scleroderma']
