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

6533b835fe1ef96bd129ea2a

RESEARCH PRODUCT

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

Andrew L. Croxford Felix J. Hartmann Pawel Pelczar Melanie Greter Margit Lanzinger Steffen Jung Florian Mair Burkhard Becher Björn E. Clausen Bettina Schreiner

subject

CCR2 Myeloid medicine.medical_treatment Interleukin-1beta Autoimmunity medicine.disease_cause Monocytes Autoimmunity Cytokine Receptor Common beta Subunit 0302 clinical medicine STAT5 Transcription Factor Immunology and Allergy Antigens Ly Myeloid Cells Phosphorylation Mice Knockout 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Experimental autoimmune encephalomyelitis Gene targeting Flow Cytometry Infectious Diseases Cytokine medicine.anatomical_structure Granulocyte macrophage colony-stimulating factor 2723 Immunology and Allergy medicine.symptom medicine.drug Signal Transduction Encephalomyelitis Autoimmune Experimental Receptors CCR2 Immunology 610 Medicine & health Inflammation Mice Transgenic Biology 03 medical and health sciences medicine Animals Humans 030304 developmental biology Inflammation 2403 Immunology Granulocyte-Macrophage Colony-Stimulating Factor 2725 Infectious Diseases Dendritic Cells medicine.disease 10040 Clinic for Neurology Immunology Transcriptome 030217 neurology & neurosurgery

description

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.

year	journal	country	edition	language
2015-09-01

http://europepmc.org/abstract/med/26341401