Dysregulation of the Cytokine GM-CSF Induces Spontaneous Phagocyte Invasion and Immunopathology in the Central Nervous System

Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Vol. 46; no. 2; p. 245
Main Authors: Spath, Sabine, Komuczki, Juliana, Hermann, Mario, Pelczar, Pawel, Mair, Florian, Schreiner, Bettina, Becher, Burkhard
Format: Journal Article
Language:English
Published: United States 21.02.2017
Subjects:
Animals
Central Nervous System - immunology
Central Nervous System - pathology
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor - immunology
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Animal
Phagocytes - immunology
Polymerase Chain Reaction
moDCs
myeloid cells
phagocytes
GM-CSF
inflammatory monocytes
multiple sclerosis
reactive oxygen species
cytokines
brain
CNS inflammation
histiocytosis
ISSN:1097-4180, 1097-4180
Online Access:Get more information
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Summary:Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral helper T (Th) cells. Antigen-independent GM-CSF release led to the invasion of inflammatory myeloid cells into the central nervous system (CNS), which was accompanied by the spontaneous development of severe neurological deficits. CNS-invading phagocytes produced reactive oxygen species and exhibited a distinct genetic signature compared to myeloid cells invading other organs. We propose that the CNS is particularly vulnerable to the attack of monocyte-derived phagocytes and that the effector functions of GM-CSF-expanded myeloid cells are in turn guided by the tissue microenvironment.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2017.01.007