GM-CSF as a therapeutic target in autoimmune diseases

Shiomi, Aoi; Usui, Takashi; Mimori, Tsuneyo

doi:10.1186/s41232-016-0014-5

Cited by 47 publications

(39 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, Th lymphocyte-derived GM-CSF was suggested to be of pivotal importance for susceptibility of distinct mouse strains to EAE [18]. Additionally, GM-CSF has attracted substantial attention as a result of the potential for antibody-mediated clinical intervention [21]. Considering all the aforementioned, it is understandable that driving factors and mechanisms underlying differentiation of GM-CSF-producing (GM-CSF+) Th lymphocytes and its role in the development of autoimmune diseases are gaining increasing attention.…”

Section: Introductionmentioning

confidence: 99%

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

et al. 2016

View full text Add to dashboard Cite

Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto)reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.

show abstract

Section: Introductionmentioning

confidence: 99%

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…There are numerous clinical trials that are attempting to target GM-CSF or the GM-CSF receptor for the treatment of autoimmune diseases [91]. One biologic that has been tested in clinical trials as an MS therapy is MOR103 [91]. MOR103 is a humanized monoclonal antibody against GM-CSF [92].…”

Section: Clinical Trials Therapeutically Targeting Gm-csfmentioning

confidence: 99%

“…Additional clinical trials will need to further evaluate the efficacy of MOR103. Although this is the only clinical trial that has assessed the use of anti-GM-CSF or GM-CSF receptor inhibitors to treat MS, there are numerous clinical trials that are attempting to utilize these biologics to treat Rheumatoid Arthritis [91]. Many of these therapeutics will likely also be tested for efficacy to treat MS in the future.…”

Section: Clinical Trials Therapeutically Targeting Gm-csfmentioning

confidence: 99%

The Role of Granulocyte-Macrophage Colony-Stimulating Factor in Murine Models of Multiple Sclerosis

Monaghan

Wan

2020

Cells

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an immune-mediated disease that predominantly impacts the central nervous system (CNS). Animal models have been used to elucidate the underpinnings of MS pathology. One of the most well-studied models of MS is experimental autoimmune encephalomyelitis (EAE). This model was utilized to demonstrate that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical and non-redundant role in mediating EAE pathology, making it an ideal therapeutic target. In this review, we will first explore the role that GM-CSF plays in maintaining homeostasis. This is important to consider, because any therapeutics that target GM-CSF could potentially alter these regulatory processes. We will then focus on current findings related to the function of GM-CSF signaling in EAE pathology, including the cell types that produce and respond to GM-CSF and the role of GM-CSF in both acute and chronic EAE. We will then assess the role of GM-CSF in alternative models of MS and comment on how this informs the understanding of GM-CSF signaling in the various aspects of MS immunopathology. Finally, we will examine what is currently known about GM-CSF signaling in MS, and how this has promoted clinical trials that directly target GM-CSF.

show abstract

“…Importantly, GM‐CSF contributes to the differentiation and pathogenesis of T‐helper (Th)17 cells . GM‐CSF also appears to be induced by Th17 cells in a model of autoimmune arthritis .…”

mentioning

confidence: 99%

“…Clinical trials of antibodies to GM‐CSF and the GM‐CSF receptor have been completed and published and show promise in rheumatoid arthritis (RA), further indicating a potential role of this cytokine in the pathogenesis of inflammatory disease . Phase III studies in RA with antibodies targeting GM‐CSF or its receptor are ongoing …”

mentioning

confidence: 99%

Targeting granulocyte‐monocyte colony‐stimulating factor in psoriasis. What a negative study can teach us

Jp¹

2019

Br J Dermatol

View full text Add to dashboard Cite

show abstract

GM-CSF as a therapeutic target in autoimmune diseases

Cited by 47 publications

References 123 publications

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

The Role of Granulocyte-Macrophage Colony-Stimulating Factor in Murine Models of Multiple Sclerosis

Targeting granulocyte‐monocyte colony‐stimulating factor in psoriasis. What a negative study can teach us

Contact Info

Product

Resources

About