| First Author | van Nieuwenhuijze AE | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 1 | Pages | 184-99 |
| PubMed ID | 24183847 | Mgi Jnum | J:206182 |
| Mgi Id | MGI:5548045 | Doi | 10.1016/j.ajpath.2013.09.014 |
| Citation | van Nieuwenhuijze AE, et al. (2014) Transgenic expression of GM-CSF in T cells causes disseminated histiocytosis. Am J Pathol 184(1):184-99 |
| abstractText | 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. |
