Phenotypic and Epigenetic Adaptations of Cord Blood CD4+ T Cells to Maternal Obesity.
Phenotypic and Epigenetic Adaptations of Cord Blood CD4+ T Cells to Maternal Obesity.
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DOI：
10.3389/fimmu.2021.617592
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发表时间：
2021
影响因子：
7.3
通讯作者：
Messaoudi I
中科院分区：
文献类型：
--
作者：
Sureshchandra S;Mendoza N;Jankeel A;Wilson RM;Marshall NE;Messaoudi I
妊娠前肥胖已被证明会破坏后代免疫系统的发育，并增加感染的易感性。虽然母体肥胖对胎儿骨髓细胞影响的潜在机制正在出现，但对T细胞的影响仍然不清楚。在这项研究中，我们收集了来自瘦母亲和肥胖母亲所生婴儿的脐带血样本，并使用流式细胞术和单细胞RNA测序在静息和体外多克隆刺激后对CD4 T细胞进行了分析。我们报告说，母亲肥胖与较高频率的记忆性CD4 T细胞提示在体内激活。此外，单细胞RNA测序揭示了与母亲肥胖的记忆T细胞的激活的子集的扩展。然而，纯化的CD4 T细胞的离体刺激导致较差的细胞因子应答，表明功能缺陷。这些表型和功能异常与淋巴细胞活化和T细胞受体信号相关基因座的甲基化和染色质可及性变化相关，表明母体致肥胖环境和胎儿免疫重编程之间可能存在联系。这些观察结果为肥胖母亲所生婴儿对微生物感染的易感性增加提供了一个潜在的解释。
Pregravid obesity has been shown to disrupt the development of the offspring’s immune system and increase susceptibility to infection. While the mechanisms underlying the impact of maternal obesity on fetal myeloid cells are emerging, the consequences for T cells remain poorly defined. In this study, we collected umbilical cord blood samples from infants born to lean mothers and mothers with obesity and profiled CD4 T cells using flow cytometry and single cell RNA sequencing at resting and following ex vivo polyclonal stimulation. We report that maternal obesity is associated with higher frequencies of memory CD4 T cells suggestive of in vivo activation. Moreover, single cell RNA sequencing revealed expansion of an activated subset of memory T cells with maternal obesity. However, ex vivo stimulation of purified CD4 T cells resulted in poor cytokine responses, suggesting functional defects. These phenotypic and functional aberrations correlated with methylation and chromatin accessibility changes in loci associated with lymphocyte activation and T cell receptor signaling, suggesting a possible link between maternal obesogenic environment and fetal immune reprogramming. These observations offer a potential explanation for the increased susceptibility to microbial infection in babies born to mothers with obesity.
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影响因子：
3.6
作者：
Griffiths PS;Walton C;Samsell L;Perez MK;Piedimonte G
通讯作者：
Piedimonte G
DOI：
10.4049/jimmunol.1301057
发表时间：
2013-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Myles IA;Fontecilla NM;Janelsins BM;Vithayathil PJ;Segre JA;Datta SK
通讯作者：
Datta SK
影响因子：
8.1
作者：
Kamimae-Lanning AN;Krasnow SM;Goloviznina NA;Zhu X;Roth-Carter QR;Levasseur PR;Jeng S;McWeeney SK;Kurre P;Marks DL
通讯作者：
Marks DL
影响因子：
32.4
作者：
Min, BK;McHugh, R;Paul, WE
通讯作者：
Paul, WE
影响因子：
6.9
作者：
Odaka, Yukino;Nakano, Mana;Sato, Kazuto
通讯作者：
Sato, Kazuto