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

Krzysztof Laudanski, Carol Miller-Graziano, Wenzhong Xiao, Michael N. Mindrinos, Daniel R. Richards, Asit De, Lyle L. Moldawer, Ronald V. Maier, Paul Bankey, Henry V. Baker, Bernard H. Brownstein, J. Perren Cobb, Steve E. Galvano, Ronald W. Davis, Ronald G. Tompkins*, Timothy R. Billiar, David Camp, Celeste Campbell-Finnerty, George Casella, Irshad H. ChaudryMashkoor Choudhry, Constance Elson, Bradley Freeman, Richard L. Gamelli, Nicole S. Gibran, Brian G. Harbrecht, Douglas L. Hayden, David N. Herndon, Jureta W. Horton, William Hubbard, John Lee Hunt, Jeffrey Johnson, Matthew B. Klein, James A. Lederer, Tanya Logvinenko, Stephen F. Lowry, John A. Mannick, Philip H. Mason, Grace P. McDonald-Smith, Bruce A. McKinley, Joseph P. Minei, Ernest E. Moore, Frederick A. Moore, Avery B. Nathens, Grant E. O'Keefe, Laurence G. Rahme, Daniel G. Remick, David A. Schoenfeld, Michael B. Shapiro, Martin Schwacha, Geoffrey M. Silver, Richard D. Smith, John Storey, Mehmet Toner, H. Shaw Warren, Michael A. West

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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

Original languageEnglish
Pages (from-to)15564-15569
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - 17 Oct 2006
Externally publishedYes


  • Anergy
  • Apoptosis
  • Costimulatory receptors
  • Immunosuppression
  • Network analysis


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