STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Transplantation
  • Graft vs Host Disease
  • Lymphocyte Activation
  • Mitogen-Activated Protein Kinase 3
  • STAT3 Transcription Factor
  • T-Lymphocytes

abstract

  • Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation, and donor T cells are indispensable for GVHD. Current therapies have limited efficacy, selectivity, and high toxicities. We used a novel flow cytometry technique for the analysis of intracellular phosphorylation events in single cells in murine BMT models to identify and validate novel GVHD drug targets.(1-7) This method circumvents the requirement for large numbers of purified cells, unlike western blots. We defined a signaling profile for alloactivated T cells in vivo and identified the phosphorylation of ERK1/2 and STAT-3 as important events during T-cell (allo)activation in GVHD. We establish that interference with STAT-3 phosphorylation can inhibit T-cell activation and proliferation in vitro and GVHD in vivo. This suggests that phospho-specific flow cytometry is useful for the identification of promising drug targets, and ERK1/2 and STAT-3 phosphorylation in alloactivated T cells may be important for GVHD.

publication date

  • December 15, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2597618

Digital Object Identifier (DOI)

  • 10.1182/blood-2008-03-147322

PubMed ID

  • 18838616

Additional Document Info

start page

  • 5254

end page

  • 8

volume

  • 112

number

  • 13