Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.
Stereotypic Expansion of T Regulatory and Th17 Cells during Infancy Is Disrupted by HIV Exposure and Gut Epithelial Damage.
复制标题
DOI：
10.4049/jimmunol.2100503
复制
发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Gray CM
中科院分区：
文献类型：
--
作者：
Dzanibe S;Lennard K;Kiravu A;Seabrook MSS;Alinde B;Holmes SP;Blish CA;Jaspan HB;Gray CM
很少有研究调查整个新生儿和儿科早期的免疫细胞个体发育，在这些阶段，感染的易感性往往增加。在这里，我们评估了两个关键的T细胞群体，调节性(Treg)细胞和Th17细胞，在人类生命的头36周内的动态。首先，我们观察了出生后12小时内采集的脐带血和外周血中不同的CD4+T细胞表型，表明脐带血不能替代新生儿血。其次，Treg和Th17细胞在36周的生命中以同步的方式扩张。然而，将宫内暴露于HIV但仍未感染的婴儿(IHEU)与未暴露于HIV的未感染对照组婴儿(IHUU)进行比较，出生时外周血Treg细胞的频率较低，导致延迟扩张，然后在36周时再次下降。聚焦于出生事件，我们发现共表达CCR4和α4β7的Treg细胞与CCR17(CCR4的配体)和肠道脂肪酸结合蛋白(IFABP)、IL-7和CCL20的血浆浓度呈负相关。这与Th17细胞相反，Th17细胞与这些血浆分析物呈正相关。因此，尽管这两个细胞亚群在出生后的最初几个月里都出现了刻板的扩张，但出生时Th17与Treg细胞的平衡发生了破坏，这可能是由于肠道损伤和新生儿Treg细胞从血液循环到肠道的归巢所致。
Few studies have investigated immune cell ontogeny throughout the neonatal and early paediatric period, where there is often increased vulnerability to infections. Here, we evaluated the dynamics of two critical T cell populations, regulatory (Treg) cells and Th17 cells, over the first 36 weeks of human life. Firstly, we observed distinct CD4+ T cells phenotypes between cord blood and peripheral blood, collected within 12 hours of birth, showing that cord blood is not a surrogate for newborn blood. Secondly, both Treg and Th17 cells expanded in a synchronous fashion over 36 weeks of life. However, comparing infants exposed to HIV in utero, but remaining uninfected (iHEU), with HIV-unexposed uninfected control infants (iHUU), there was a lower frequency of peripheral blood Treg cells at birth, resulting in a delayed expansion, and then declining again at 36 weeks. Focusing on birth events, we found that Treg cells co-expressing CCR4 and α4β7 inversely correlated with plasma concentrations of CCL17 (the ligand for CCR4) and intestinal fatty acid binding protein (iFABP), IL-7 and CCL20. This was in contrast to Th17 cells, which showed a positive association with these plasma analytes. Thus, despite the stereotypic expansion of both cell subsets over the first few months of life, there was a disruption in the balance of Th17 to Treg cells at birth likely being a result of gut damage and homing of newborn Treg cells from the blood circulation to the gut.
登录
查看更多内容
影响因子：
17.1
作者：
Ardeshir A;Narayan NR;Méndez-Lagares G;Lu D;Rauch M;Huang Y;Van Rompay KK;Lynch SV;Hartigan-O'Connor DJ
通讯作者：
Hartigan-O'Connor DJ
影响因子：
20.3
作者：
Clerici, M;Saresella, M;Vigano, A
通讯作者：
Vigano, A
影响因子：
7.3
作者：
Jalbert, Emilie;Williamson, Kayla M.;Weinberg, Adriana
通讯作者：
Weinberg, Adriana
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
30.3
作者：
Backhed, Fredrik;Roswall, Josefine;Jun, Wang
通讯作者：
Jun, Wang