Document Type

Article

Publication Date

1-31-2020

Comments

This article is the author’s final published version in Scientific Reports, Volume 10, Issue 1, January 2020, Article number 1567.

The published version is available at https://doi.org/10.1038/s41598-020-58131-2. Copyright © Lotfi et al.

Abstract

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

32005854

Language

English

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