Author:
Spivey Tara L,Uccellini Lorenzo,Ascierto Maria Libera,Zoppoli Gabriele,De Giorgi Valeria,Delogu Lucia Gemma,Engle Alyson M,Thomas Jaime M,Wang Ena,Marincola Francesco M,Bedognetti Davide
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference198 articles.
1. Panelli MC, Stashower ME, Slade HB, Smith K, Norwood C, Abati A, Fetsch P, Filie A, Walters SA, Astry C: Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection. Genome Biology. 2007, 8:
2. Wang E, Miller LD, Ohnmacht GA, Mocellin S, Perez-Diaz A, Petersen D, Zhao YD, Simon R, Powell JI, Asaki E: Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness. Cancer Research. 2002, 62: 3581-3586.
3. Wang E, Worschech A, Marincola FM: The immunologic constant of rejection. Trends in Immunology. 2008, 29: 256-262.
4. Bedognetti D, Wang E, Sertoli MR, Marincola FM: Gene-expression profiling in vaccine therapy and immunotherapy for cancer. Expert Review of Vaccines. 2010, 9: 555-565.
5. Imanguli MM, Swaim WD, League SC, Gress RE, Pavletic SZ, Hakim FT: Increased T-bet+ cytotoxic effectors and type I interferon-mediated processes in chronic graft-versus-host disease of the oral mucosa. Blood. 2009, 113: 3620-3630.
Cited by
82 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献