Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. In addition to its effects as a growth factor, GM-CSF plays an important role in chronic inflammatory autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Reports have identified monocytes as the primary target of GM-CSF; however, its effect on monocyte activation has been under-estimated. Here, using flow cytometry and ELISA we show that GM-CSF induces an inflammatory profile in human monocytes, which includes an upregulated expression of HLA-DR and CD86 molecules and increased production of TNF-α and IL-1β. Conversely, blockage of endogenous GM-CSF with antibody treatment not only inhibited the inflammatory profile of these cells, but also induced an immunomodulatory one, as shown by increased IL-10 production by monocytes. Further analysis with qPCR, flow cytometry and ELISA experiments revealed that GM-CSF blockage in monocytes stimulated production of the chemokine CXCL-11, which suppressed T cell proliferation. Blockade of CXCL-11 abrogated anti-GM-CSF treatment and induced inflammatory monocytes. Our findings show that anti-GM-CSF treatment induces modulatory monocytes that act in a CXCL-11-dependent manner, a mechanism that can be used in the development of novel approaches to treat chronic inflammatory autoimmune diseases.
Lotfi, Noushin; Zhang, Guang-Xian; Esmaeil, Nafiseh; and Rostami, Mohamad, "Evaluation of the effect of GM-CSF blocking on the phenotype and function of human monocytes." (2020). Department of Neurology Faculty Papers. Paper 215.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
This is the final version of the article published in Scientific Reports, Volume 10, Issue 1: 1567
The published version is available at https://doi.org/10.1038/s41598-020-58131-2.
Copyright Lotfi et.al.