Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Department of Ophthalmology and Biochemistry & Molecular Biology, St. Louis University School of Medicine, Saint Louis, MO 63104, USA.
Biomolecules. 2023 Sep 22;13(10):1432. doi: 10.3390/biom13101432.
Autoimmune diseases caused by T cells can arise from either T-helper 1 (Th1) or T-helper 17 (Th17)-type pathogenic T cells. However, it is unclear whether these two T-cell subsets are influenced by distinct pathogenic factors and whether treatments that are effective for Th1 responses also work for Th17 responses. To compare these two pathogenic responses, we conducted a systematic analysis in a mouse model of experimental autoimmune uveitis (EAU) to identify the factors that promote or inhibit each response and to determine their responses to various treatments. Our study found that the two types of pathogenic responses differ significantly in their pathological progressions and susceptibility to treatments. Specifically, we observed that extracellular adenosine is a crucial pathogenic molecule involved in the pathogenicity of inflammation and T-cell reactivity and that reciprocal interaction between adenosine and gamma delta (γδ) T cells plays a significant role in amplifying Th17 responses in the development of autoimmune diseases. The potential effect of targeting adenosine or adenosine receptors is analyzed regarding whether such targeting constitutes an effective approach to modulating both γδ T-cell responses and the pathogenic Th17 responses in autoimmune diseases.
自身免疫性疾病由 T 细胞引起，可以源自辅助性 T 细胞 1（Th1）或辅助性 T 细胞 17（Th17）型致病性 T 细胞。然而，尚不清楚这两种 T 细胞亚群是否受到不同的致病因素影响，以及对 Th1 反应有效的治疗方法是否也适用于 Th17 反应。为了比较这两种致病反应，我们在实验性自身免疫性葡萄膜炎（EAU）的小鼠模型中进行了系统分析，以确定促进或抑制每种反应的因素，并确定它们对各种治疗方法的反应。我们的研究发现，两种类型的致病反应在病理进展和对治疗的敏感性方面存在显著差异。具体而言，我们观察到细胞外腺苷是一种关键的致病分子，参与炎症和 T 细胞反应的致病性，腺苷与γδ（γδ）T 细胞之间的相互作用在自身免疫性疾病中放大 Th17 反应的发展中起着重要作用。分析了针对腺苷或腺苷受体的潜在影响，以确定这种靶向是否构成调节 γδ T 细胞反应和自身免疫性疾病中致病性 Th17 反应的有效方法。
