Transgenic Expression of GM-CSF in T Cells Causes Disseminated Histiocytosis.
- Author(s)
- van Nieuwenhuijze, Annemarie E; Coghill, Elise; Gray, Daniel; Prato, Sandro; Metcalf, Donald; Alexander, Warren S; Wicks, Ian P;
- Details
- Publication Year 2014-01,Volume 184,Issue #1,Page 184-199
- Journal Title
- The American journal of pathology
- Publication Type
- Journal Article
- Abstract
- Recent studies highlight surprising roles for granulocyte-macrophage colony-stimulating factor (GM-CSF) production by T cells. T-cell-derived GM-CSF is required for the differentiation of monocyte-derived inflammatory dendritic cells during inflammation and for the pathogenicity of IL-17 producing T helper cells in autoimmunity. To gain further insight into these findings, we engineered in vivo overexpression of GM-CSF specifically in T cells, under the control of the Lck promoter. Lck-GM-CSF transgenic mice displayed a dramatic phenotype, characterized by splenomegaly, lymphadenopathy, thymic atrophy, and multiple abnormalities in blood cell populations. Thymocyte differentiation was severely affected, and there was a dramatic increase in regulatory T cells in the thymus and peripheral lymphoid organs. Lck-GM-CSF transgenic mice developed a disseminated histiocytosis and had increased circulating IL-17 producing T helper cells-related cytokines. The pathological characteristics in Lck-GM-CSF transgenic mice resemble those of histiocytic human diseases, such as Langerhans cell histiocytosis. The etiology of many histiocytic disorders is unknown, but our findings suggest that over-production of GM-CSF by T cells could be a pathogenic factor and raise the possibility that GM-CSF may represent a novel therapeutic target.
- Publisher
- Elsevier
- Research Division(s)
- Cancer And Haematology; Inflammation; Molecular Genetics Of Cancer; Immunology
- Publisher's Version
- https://doi.org/10.1016/j.ajpath.2013.09.014
- Terms of Use/Rights Notice
- Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Creation Date: 2014-01-16 04:26:29