Aram Jehan, Frakich Nanci, Morandi Elena, Alrouji Mohammed, Samaraweera Amal, Onion David, Spendlove Ian, Colombo Sergio L, Tanasescu Radu, Gran Bruno, Constantinescu Cris S
Division of Clinical Neuroscience, Section of Clinical Neurology, University of Nottingham, Nottingham NG7 2UH, UK.
Inserm, Centre de Physiopathologie de Toulouse Purpan (CPTP), 31300 Toulouse, France.
Biomedicines. 2020 Jul 18;8(7):226. doi: 10.3390/biomedicines8070226.
Granulocyte macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine produced by immune cells. Recent evidence suggests that GM-CSF plays an important role in multiple sclerosis (MS) pathogenesis. We investigated the expression and regulation of GM-CSF in different immune cells in MS. We also investigated the differentiation and frequency of GM-CSF-producing Th cells that do not co-express interferon (IFN)-γ or interleukin-17 (IL-17) (Th-GM cells) in MS. We found a significant increase in the percentage of GM-CSF-expressing Th cells, Th1 cells, Th-GM cells, cytotoxic T (Tc) cells, monocytes, natural killer (NK) cells, and B cells in PBMC from MS patients stimulated with T cell stimuli. Stimulated PBMC culture supernatants from MS patients contained significantly higher levels of IL-2, IL-12, IL-1β, and GM-CSF and significantly lower levels of transforming growth factor (TGF-)β. Blocking IL-2 reduced the frequency of Th-GM cells in PBMC from MS patients. The frequency of Th-GM cells differentiated in vitro from naïve CD4 T cells was significantly higher in MS patients and was further increased in MS with IL-2 stimulation. These findings suggest that all main immune cell subsets produce more GM-CSF in MS after in vitro stimulation, which is associated with defective TGF-β and increased IL-2 and IL-12 production. Th-GM cells are increased in MS. GM-CSF may be a potential therapeutic target in MS.
粒细胞巨噬细胞集落刺激因子（GM-CSF）是一种由免疫细胞产生的促炎细胞因子。最近的证据表明，GM-CSF在多发性硬化症（MS）发病机制中起重要作用。我们研究了GM-CSF在MS不同免疫细胞中的表达和调控。我们还研究了MS中不共表达干扰素（IFN）-γ或白细胞介素-17（IL-17）的产生GM-CSF的Th细胞（Th-GM细胞）的分化和频率。我们发现，在用T细胞刺激剂刺激的MS患者外周血单个核细胞（PBMC）中，表达GM-CSF的Th细胞、Th1细胞、Th-GM细胞、细胞毒性T（Tc）细胞、单核细胞、自然杀伤（NK）细胞和B细胞的百分比显著增加。MS患者受刺激的PBMC培养上清液中IL-2、IL-12、IL-1β和GM-CSF水平显著升高，而转化生长因子（TGF）-β水平显著降低。阻断IL-2可降低MS患者PBMC中Th-GM细胞的频率。MS患者中，从初始CD4 T细胞体外分化的Th-GM细胞频率显著更高，并且在IL-2刺激下在MS中进一步增加。这些发现表明，在体外刺激后，MS中所有主要免疫细胞亚群产生更多的GM-CSF，这与TGF-β缺陷以及IL-2和IL-12产生增加有关。MS中Th-GM细胞增加。GM-CSF可能是MS的一个潜在治疗靶点。
