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Immunity. 2015 Sep 15;43(3):502-14. doi: 10.1016/j.immuni.2015.08.010. Epub 2015 Sep 1.

The Cytokine GM-CSF Drives the Inflammatory Signature of CCR2+ Monocytes and Licenses Autoimmunity.

Author information

1
Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
2
Institute for Molecular Medicine, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
3
Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel.
4
Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland. Electronic address: becher@immunology.uzh.ch.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation. Multiple cell types can sense GM-CSF, but the identity of the pathogenic GM-CSF-responsive cells is unclear. By using conditional gene targeting, we systematically deleted the GM-CSF receptor (Csf2rb) in specific subpopulations throughout the myeloid lineages. Experimental autoimmune encephalomyelitis (EAE) progressed normally when either classical dendritic cells (cDCs) or neutrophils lacked GM-CSF responsiveness. The development of tissue-invading monocyte-derived dendritic cells (moDCs) was also unperturbed upon Csf2rb deletion. Instead, deletion of Csf2rb in CCR2(+)Ly6C(hi) monocytes phenocopied the EAE resistance seen in complete Csf2rb-deficient mice. High-dimensional analysis of tissue-infiltrating moDCs revealed that GM-CSF initiates a combination of inflammatory mechanisms. These results indicate that GM-CSF signaling controls a pathogenic expression signature in CCR2(+)Ly6C(hi) monocytes and their progeny, which was essential for tissue damage.

PMID:
26341401
DOI:
10.1016/j.immuni.2015.08.010
[Indexed for MEDLINE]
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