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Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2021-09-23 , DOI: 10.3389/fimmu.2021.726472
Aloysious Ssemaganda 1 , Francois Cholette 1, 2 , Michelle Perner 1 , Cheli Kambaran 1 , Wendy Adhiambo 3 , Peter M Wambugu 3 , Henok Gebrebrhan 1 , Amy Lee 1 , Faisal Nuhu 1 , Ruth S Mwatelah 1 , Naima Jahan 1 , Tosin E Omole 1 , Tabitha Wanjiru 3 , Apollo Gitau 3 , Joshua Kimani 1, 3 , Lyle R McKinnon 1, 2, 4
Affiliation  

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.



中文翻译:

子宫颈管调节性 T 细胞与减少生殖器炎症和降低 HIV 靶细胞丰度有关

调节性 T 细胞 (Tregs) 在组织稳态中发挥重要作用,但很少有研究在人类生殖器炎症、HIV 靶细胞密度和阴道微生物群的背景下研究组织 Tregs。在来自内罗毕的女性 (n=64) 中,子宫颈内膜中 CD4+ CD25+ CD127Treg的比例与血液中的相关 (r=0.31, p=0.01),在子宫颈内观察到的 Treg 频率更高(中位数 3.8对比2.0%,p<0.0001)。大多数 Tregs 在两个隔室中都表达 FOXP3,与血液相比,宫颈内 Tregs 上的 CTLA-4 表达更高(中位数 50.8对比6.0%,p<0.0001)。超过一半 (34/62, 55%) 的参与者表现出非乳酸菌占优势的阴道微生物群,与宫颈内 Treg 或 CD4+ T 细胞丰度无关。在多变量线性回归中,宫颈内 Treg 比例与促炎细胞因子升高的数量呈负相关(p = 0.03)。还观察到了特定细胞因子的反向 Treg 关联,包括 IL-1β、G-CSF、嗜酸性粒细胞趋化因子、IL-1RA、IL-8 和 MIP-1β。较高的宫颈内 Treg 比例与较低的宫颈内 CD4+ T 细胞丰度相关(0.30 log 10 CD4+ T 细胞/log 10 Treg,p=0.00028),Th17 细胞的趋势相似(p=0.09)。选择性增加宫颈内 Tregs 可能代表减少女性生殖道炎症的途径。

更新日期:2021-09-23
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