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Gene expression profiling in acute allograft rejection: challenging the immunologic constant of rejection hypothesis

Spivey, Tara L. and Uccellini, Lorenzo and Ascierto, Maria Libera and Zoppoli, Gabriele and De Giorgi, Valeria and Delogu, Lucia Gemma and Engle, Alyson M. and Thomas, Jaime M. and Wang, Ena and Marincola, Francesco M. and Bedognetti, Davide (2011) Gene expression profiling in acute allograft rejection: challenging the immunologic constant of rejection hypothesis. Journal of Translational Medicine, Vol. 9 (174), p. 1-22. eISSN 1479-5876. Article.

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DOI: 10.1186/1479-5876-9-174


In humans, the role and relationship between molecular pathways that lead to tissue destruction during acute allograft rejection are not fully understood. Based on studies conducted in humans, we recently hypothesized that different immune-mediated tissue destruction processes (i.e. cancer, infection, autoimmunity) share common convergent final mechanisms. We called this phenomenon the "Immunologic Constant of Rejection (ICR)." The elements of the ICR include molecular pathways that are consistently described through different immune-mediated tissue destruction processes and demonstrate the activation of interferon-stimulated genes (ISGs), the recruitment of cytotoxic immune cells (primarily through CXCR3/CCR5 ligand pathways), and the activation of immune effector function genes (IEF genes; granzymes A/B, perforin, etc.).
Here, we challenge the ICR hypothesis by using a meta-analytical approach and systematically reviewing microarray studies evaluating gene expression on tissue biopsies during acute allograft rejection. We found the pillars of the ICR consistently present among the studies reviewed, despite implicit heterogeneity.
Additionally, we provide a descriptive mechanistic overview of acute allograft rejection by describing those molecular pathways most frequently encountered and thereby thought to be most significant. The biological role of the following molecular pathways is described: IFN-γ, CXCR3/CCR5 ligand, IEF genes, TNF-α, IL-10, IRF-1/STAT-1, and complement pathways. The role of NK cell, B cell and T-regulatory cell signatures are also addressed.

Item Type:Article
ID Code:7613
Uncontrolled Keywords:Gene expression profiling, acute allograft rejection, Immunologic Constant of Rejection (ICR)
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:BioMed Central
Copyright Holders:© 2011 Spivey et al; licensee BioMed Central Ltd.
Deposited On:23 May 2012 12:05

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