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

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 condition...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Immunity (Cambridge, Mass.) Ročník 43; číslo 3; s. 502
Hlavní autori:	Croxford, Andrew L, Lanzinger, Margit, Hartmann, Felix J, Schreiner, Bettina, Mair, Florian, Pelczar, Pawel, Clausen, Björn E, Jung, Steffen, Greter, Melanie, Becher, Burkhard
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 15.09.2015
Predmet:	Animals Antigens, Ly - genetics Antigens, Ly - immunology Antigens, Ly - metabolism Autoimmunity - genetics Autoimmunity - immunology Cytokine Receptor Common beta Subunit - genetics Cytokine Receptor Common beta Subunit - immunology Cytokine Receptor Common beta Subunit - metabolism Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Encephalomyelitis, Autoimmune, Experimental Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor - immunology Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Humans Inflammation - genetics Inflammation - immunology Inflammation - metabolism Interleukin-1beta - genetics Interleukin-1beta - immunology Interleukin-1beta - metabolism Mice, Knockout Mice, Transgenic Monocytes - drug effects Monocytes - immunology Monocytes - metabolism Myeloid Cells - drug effects Myeloid Cells - immunology Myeloid Cells - metabolism Phosphorylation - drug effects Phosphorylation - immunology Receptors, CCR2 - genetics Receptors, CCR2 - immunology Receptors, CCR2 - metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction - drug effects Signal Transduction - genetics Signal Transduction - immunology STAT5 Transcription Factor - immunology STAT5 Transcription Factor - metabolism Transcriptome - drug effects Transcriptome - genetics Transcriptome - immunology
ISSN:	1097-4180, 1097-4180
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4180 1097-4180
DOI:	10.1016/j.immuni.2015.08.010