Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways

• DOI: 10.1073/pnas.0607028103
• Publication Date: 2006-10-11T02:54:28Z
• Authors: Krzysztof Laudanski; Carol Miller-Graz...; Wenzhong Xiao; Michael N. Mindrinos; Daniel R. Richards; Asit De; Lyle L. Moldawer; Ronald V. Maier; Paul Bankey; Henry V. Baker; Bernard H. Browns...; J. Perren Cobb; Steve E. Calvano; Ronald W. Davis; Ronald G. Tompkins
• Keywords: Monocyte

Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough develop multiple organ dysfunction syndrome have immune derangements, including T cell apoptosis and anergy combined depressed monocyte antigen presentation. Genome-wide expression analysis highly enriched circulating leukocyte subpopulations, pathway analyses, offers an opportunity discover regulatory networks in critically injured patients. Severe injury induced significant changes (5,693 genes), (2,801 total (3,437 genes) transcriptomes, only 911 these genes common all three populations (12%). analyses identified increased gene several inhibitory receptors (PD-1, CD152, NRP-1, Lag3) concomitant decreases stimulatory (CD28, CD4, IL-2Ralpha). Functional cells monocytes confirmed reduced proliferation surface negative signaling paired decreased costimulation ligands. Thus, genome-wide from knowledge-based leads identification differentially expressed Importantly, application separation, expression, can be used alterations disease.