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Immunity. 2017 Feb 21;46(2):245-260. doi: 10.1016/j.immuni.2017.01.007.

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

Author information

1
Institute of Experimental Immunology, Inflammation Research, University of Zurich, 8057 Zurich, Switzerland.
2
Institute of Laboratory Animal Science, University of Zurich, 8091 Zurich, Switzerland; Institute of Neuropathology, University Hospital Zurich, 8091 Zurich, Switzerland.
3
Institute of Laboratory Animal Science, University of Zurich, 8091 Zurich, Switzerland.
4
Institute of Experimental Immunology, Inflammation Research, University of Zurich, 8057 Zurich, Switzerland; Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland. Electronic address: schreiner@immunology.uzh.ch.
5
Institute of Experimental Immunology, Inflammation Research, University of Zurich, 8057 Zurich, Switzerland. Electronic address: becher@immunology.uzh.ch.

Abstract

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.

KEYWORDS:

CNS inflammation; GM-CSF; brain; cytokines; histiocytosis; inflammatory monocytes; moDCs; multiple sclerosis; myeloid cells; phagocytes; reactive oxygen species

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PMID:
28228281
DOI:
10.1016/j.immuni.2017.01.007
[Indexed for MEDLINE]
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