Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Conversely, a protective role has also been described in other autoimmune diseases where humoral responses are detrimental such as myasthenia gravis (MG), Hashimoto's thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE). In this review, we aimed for a comprehensive analysis of literature data on the multiple roles of GM-CSF in autoimmue diseases and possible therapeutic strategies that target GM-CSF production.

The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

“…GM-CSF is upstream of IL-6 and induces an inflammatory transcriptional program through JAK/ STAT signaling. 101 Inactivation of GM-CSF in CAR T on June 9, 2020 by guest. Protected by copyright.…”

“…Although the safety profiles of anti-GM-CSF antibodies have been acceptable in phase I and phase II trials, it is important to note the potential for lung toxicities and pneumonia with these agents. 101 ► Lenzilumab (Humanigen) is a human monoclonal anti-GM-CSF antibody approved for compassionate use in patients with COVID-19. A phase III trial for COVID-19 is ongoing.…”

Association Between Systemic Lupus Erythematosus and Myasthenia Gravis: Coincidence or Sequelae?

“…Granulocyte-macrophage colony-stimulating factor (GM-CSF), found endogenously as well as exogenously, is a common factor between the two autoimmune diseases. It can be produced endogenously by various cell types, for example, T cells, B cells, monocytes, macrophages, mast cells, fibroblasts, vascular endothelial cells [30]. At the same time, exogenous GM-CSF is used as a treatment to help synthesize bone marrow-derived macrophages and granulocytes [30].…”

Biological disease‐modifying drugs for rheumatoid arthritis

“…Clinicians noted that treatment with GM‐CSF was sometimes associated with disease flare in patients with rheumatoid arthritis 36 . Subsequent research indicated that GM‐CSF is another cytokine contributing to the pathogenesis of rheumatoid arthritis, 37,38 and therefore a potentially important target for monoclonal antibodies.…”