Granulocyte–macrophage colony-stimulating factor (GM-CSF), an important cytokine in the development and progression of inflammatory arthritis, is produced by a variety of different cells including T helper 17 (TH17) cells, well-known contributors to arthritis pathology. “We have demonstrated that a non-T cell source of GM-CSF is indispensable for the development of autoimmune arthritis and highlighted GM-CSF-producing synovial innate lymphoid cells (ILCs) as a previously unappreciated population in inflamed joints,” reports Keiji Hirota, co-corresponding author of a new study published in Immunity.
To investigate the various sources of GM-CSF and their contribution to autoimmune pathology, Hirota and colleagues used SKG mice, a model of spontaneous T cell-mediated autoimmune arthritis. As expected, GM-CSF-deficient mice were highly resistant to disease induction. Using an adoptive T cell transfer system, they showed that although GM-CSF production by T cells augmented chronic inflammation, this process was dispensable for arthritis initiation.
... although GM-CSF production by T cells augmented chronic inflammation, this process was dispensable for arthritis initiation
Instead, GM-CSF production by radio-resistant stromal cells, including fibroblast-like synoviocytes (FLSs) and ILCs, was crucial for the development of autoimmunity. In vitro, FLSs secreted GM-CSF in response to recombinant IL-17, whereas ILCs produced GM-CSF in response to IL-2, IL-33 and Toll-like receptor 9 (TLR9) ligands. Thus, various mechanisms can contribute to the production of this pathogenic cytokine.
“GM-CSF-producing synovial ILCs were present in the inflamed joints of SKG mice and patients with rheumatoid arthritis (RA), augmenting the disease,” explains Hirota. ILCs of a similar phenotype were present in the joints of healthy C57/BL6 mice, and this population expanded following induction of collagen-induced arthritis (another model of RA).
“Our findings provide new insight into our understanding of the cellular sources of GM-CSF and the inflammatory cascade instigated by autoimmune TH17 cells,” says co-corresponding author Shimon Sakaguchi. “Targeting this pathway might be a key therapeutic strategy for the treatment of autoimmune diseases including RA.”
References
Original article
Hirota, K. et al. Autoimmune Th17 Cells induced synovial stromal and innate lymphoid cell secretion of the cytokine GM-CSF to initiate and augment autoimmune. Immunity. https://doi.org/10.1016/j.immuni.2018.04.009 (2018)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
McHugh, J. A cellular cascade of GM-CSF production. Nat Rev Rheumatol 14, 386 (2018). https://doi.org/10.1038/s41584-018-0038-0
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41584-018-0038-0