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人类 CD3 T 淋巴细胞的氧化脂类分泌受外源性必需脂肪酸比例和生命阶段的影响。

Oxylipin secretion by human CD3 T lymphocytes is modified by the exogenous essential fatty acid ratio and life stage.

机构信息

School of Chemistry and Chemical Engineering, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, United Kingdom.

出版信息

Front Immunol. 2023 Jun 14;14:1206733. doi: 10.3389/fimmu.2023.1206733. eCollection 2023.

Abstract

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation. A number of PUFAs are precursors to oxylipins, including the essential fatty acids (EFAs) linoleic acid (LA) and α-linolenic acid (ALA). LA and ALA are also substrates for synthesis of longer chain PUFAs. Studies with stable isotopes have shown that the relative amounts of LA and ALA can influence their partitioning by T lymphocytes between conversion to longer chain PUFAs and to oxylipins. It is not known whether the relative availability of EFA substrates influences the overall pattern of oxylipin secretion by human T cells or if this changes across the life stages. To address this, the oxylipin profile was determined in supernatants from resting and mitogen activated human CD3 T cell cultures incubated in medium containing an EFA ratio of either 5:1 or 8:1 (LA : ALA). Furthermore, oxylipin profiles in supernatants of T cells from three life stages, namely fetal (derived from umbilical cord blood), adults and seniors, treated with the 5:1 EFA ratio were determined. The extracellular oxylipin profiles were affected more by the EFA ratio than mitogen stimulation such that n-3 PUFA-derived oxylipin concentrations were higher with the 5:1 EFA ratio than the 8:1 ratio, possibly due to PUFA precursor competition for lipoxygenases. 47 oxylipin species were measured in all cell culture supernatants. Extracellular oxylipin concentrations were generally higher for fetal T cells than for T cells from adult and senior donors, although the composition of oxylipins was similar across the life stages. The contribution of oxylipins towards an immunological phenotype might be due to the capacity of T cells to synthesize oxylipins rather than the nature of the oxylipins produced.

摘要

免疫功能在生命各阶段发生变化;例如,老年人表现出比年轻人更弱的细胞介导免疫反应和更强的炎症反应趋势。这可能部分是由生命过程中氧化脂质合成的变化所介导的。氧化脂质是多不饱和脂肪酸(PUFA)的氧化产物,可调节免疫功能和炎症。许多 PUFAs 是氧化脂质的前体,包括必需脂肪酸(EFA)亚油酸(LA)和α-亚麻酸(ALA)。LA 和 ALA 也是长链 PUFAs 合成的底物。使用稳定同位素的研究表明,LA 和 ALA 的相对含量可以影响 T 淋巴细胞将其转化为长链 PUFAs 和氧化脂质的分配。目前尚不清楚 EFA 底物的相对可用性是否会影响人 T 细胞氧化脂质分泌的总体模式,或者这种模式是否会随着生命阶段的变化而变化。为了解决这个问题,测定了在含有 EFA 比为 5:1 或 8:1(LA:ALA)的培养基中培养的静止和有丝分裂原激活的人 CD3 T 细胞培养物上清液中的氧化脂质谱。此外,还测定了用 5:1 EFA 比处理的来自胎儿(源自脐带血)、成人和老年人三个生命阶段的 T 细胞上清液中的氧化脂质谱。细胞外氧化脂质谱受 EFA 比的影响大于有丝分裂原刺激,使得 n-3 PUFA 衍生的氧化脂质浓度在 5:1 EFA 比下高于 8:1 比,可能是由于 PUFA 前体对脂氧合酶的竞争。在所有细胞培养上清液中测量了 47 种氧化脂质。胎儿 T 细胞的细胞外氧化脂质浓度通常高于成人和老年供体的 T 细胞,尽管氧化脂质的组成在生命各阶段相似。氧化脂质对免疫表型的贡献可能归因于 T 细胞合成氧化脂质的能力,而不是产生的氧化脂质的性质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0d4/10300345/1ff2e0d30f87/fimmu-14-1206733-g001.jpg

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