Repeated social defeat stress leads to immunometabolic shifts in innate immune cells of the spleen.
Repeated social defeat stress leads to immunometabolic shifts in innate immune cells of the spleen.
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DOI：
10.1016/j.bbih.2023.100690
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发表时间：
2023-12
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影响因子：
--
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心理社会应激已被证明是启动外周天然免疫细胞的基础，这些细胞具有高度炎症的表型，并与小鼠模型中的抑郁样行为有关。然而，应激对被认为是免疫细胞炎症表型的细胞代谢状态的影响尚不清楚。应用单细胞RNA测序技术，研究了反复社会失败应激(RSDs)和无应激(NS)小鼠脾固有免疫细胞免疫代谢途径的基因表达。与NS仔鼠相比，RSDS小鼠的脾巨噬细胞和粒细胞数量显著增加(P<0.05)。巨噬细胞、单核细胞和粒细胞中RSD上调的基因显著丰富了被认为在髓样细胞驱动的炎症(糖酵解、HIF-1信号、mTORC1信号)以及与氧化磷酸化(OXPHOS)和氧化应激相关的途径中发挥作用的免疫代谢途径(p>0.05和fdr<；0.1)。这些结果表明，糖酵解和OXPHOS途径上调所反映的代谢增强可能是反复应激后脾巨噬细胞和粒细胞增殖的重要因素。更好地了解这些细胞内代谢机制最终可能有助于开发新的策略，以逆转压力和相关的外周免疫变化对大脑和行为的影响。应激后促进免疫细胞激活的代谢变化尚不清楚。ScRNA-Seq比较了反复社交失败(RSD)小鼠和对照组小鼠的脾细胞。RSD可使小鼠脾内单核/巨噬细胞和粒细胞数量增多。与髓系炎症有关的代谢途径在RSD中丰富。糖酵解途径可能使应激暴露后的脾骨髓生成。
Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p < 0.05) compared to NS littermates. RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). These results suggest that the metabolic enhancement reflected by upregulation of glycolytic and OXPHOS pathways may be important for cellular proliferation of splenic macrophages and granulocytes following repeated stress exposure. A better understanding of these intracellular metabolic mechanisms may ultimately help develop novel strategies to reverse the impact of stress and associated peripheral immune changes on the brain and behavior. Metabolic shifts that facilitate immune cell activation following stress are unknown. scRNA-Seq compared splenocytes of repeated social defeat (RSDS) and control mice. RSDS led to greater monocyte/macrophage and granulocyte abundance in the spleen. Metabolic pathways implicated in myeloid-driven inflammation were enriched in RSDS. Glycolytic pathways may enable splenic myelopoiesis following stress exposure.
影响因子：
5
作者：
Bekhbat, Mandakh;Ulukaya, G. Bengu;Bhasin, Manoj K.;Felger, Jennifer C.;Miller, Andrew H.
通讯作者：
Miller, Andrew H.
影响因子：
3
作者：
Ambrée O;Ruland C;Scheu S;Arolt V;Alferink J
通讯作者：
Alferink J