Chapter 10 - Micro-RNA and Kinase Regulatory Mechanisms and Pathways in GVHD

Abstract

Proinflammatory pathways that become activated during graft-versus-host disease (GVHD) are regulated by micro-RNAs (miRs) and kinases. miRs are small endogenous noncoding RNAs that post-transcriptionally regulate gene expression and thereby impact inflammatory events at multiple levels. Kinases mediate the downstream effects of multiple cell-biological events required for alloreactivity including cytokine receptor, chemokine receptors signaling, cell-cycle progression, filament stabilization, and migratory activity. While multiple inflammation-related miR target genes are described, there is increasing evidence that the same miR can have different effects by preferentially targeting certain genes depending on the cell type in which the miR is analyzed. Besides their functional role in GVHD and graft-versus-leukemia effects (GVL), miR levels in different body fluids could function as biomarkers and help to predict or diagnose GVHD, thereby guiding clinical decision-making. This chapter describes the pleomorphic function of miRs and kinases as potent regulators of multiple pro- or anti-inflammatory target genes and signaling pathways for GVHD, respectively. A better understanding of the miR and kinase biology may help to manipulate GVHD and GVL effects.