[PDF][PDF] The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity

AL Croxford, M Lanzinger, FJ Hartmann, B Schreiner… - Immunity, 2015 - cell.com
AL Croxford, M Lanzinger, FJ Hartmann, B Schreiner, F Mair, P Pelczar, BE Clausen, S Jung…
Immunity, 2015cell.com
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 …
Summary
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+Ly6Chi 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+Ly6Chi monocytes and their progeny, which was essential for tissue damage.
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