https://ror.org/03v76x132 Departments of Neurology and Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
https://ror.org/050gn5214 Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, APHP, Hôpital de la Pitié-Salpêtrière, Paris, France.
Life Sci Alliance. 2024 Oct 4;7(12). doi: 10.26508/lsa.202402890. Print 2024 Dec.
IFNγ-secreting T cells are central for the maintenance of immune surveillance within the central nervous system (CNS). It was previously reported in healthy donors that the T-cell environment in the CNS induces distinct signatures related to cytotoxic capacity, CNS trafficking, tissue adaptation, and lipid homeostasis. These findings suggested that the CNS milieu consisting predominantly of lipids mediated the metabolic conditions leading to IFNγ-secreting brain CD4 T cells. Here, we demonstrate that the supplementation of CD4CD45ROCXCR3 cells with cholesterol modulates their function and increases expression. The heightened expression was mediated by the activation of the serum/glucocorticoid-regulated kinase (SGK1). Inhibition of SGK1 by a specific enzymatic inhibitor significantly reduces the expression of Our results confirm the crucial role of lipids in maintaining T-cell homeostasis and demonstrate a putative role of environmental factors to induce effector responses in CD4 effector/memory cells. These findings offer potential avenues for further research targeting lipid pathways to modulate inflammatory conditions.
IFNγ 分泌 T 细胞是中枢神经系统 (CNS) 中免疫监视的核心。先前有报道称，在健康供体中，CNS 中的 T 细胞环境诱导与细胞毒性能力、CNS 迁移、组织适应和脂质稳态相关的独特特征。这些发现表明，主要由脂质组成的 CNS 环境介导了导致 IFNγ 分泌脑 CD4 T 细胞的代谢条件。在这里，我们证明用胆固醇补充 CD4CD45ROCXCR3 细胞可调节其功能并增加 的表达。 的高表达是通过激活血清/糖皮质激素调节激酶 (SGK1) 介导的。通过特异性酶抑制剂抑制 SGK1 可显著降低 的表达。我们的结果证实了脂质在维持 T 细胞动态平衡中的关键作用，并证明了环境因素在诱导 CD4 效应器/记忆细胞效应反应中的潜在作用。这些发现为进一步研究靶向脂质途径调节炎症条件提供了潜在途径。
