Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle.
Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle.
复制标题
DOI：
10.3389/fendo.2021.721813
复制
发表时间：
2021
影响因子：
5.2
通讯作者：
Nalvarte I
中科院分区：
文献类型：
--
作者：
Brundin PMA;Landgren BM;Fjällström P;Shamekh MM;Gustafsson JÅ;Johansson AF;Nalvarte I
已知性激素在多个水平上与免疫系统相互作用，但关于性激素受体（SHR）的类型及其在免疫细胞中的表达水平的信息很少。雌激素、睾酮和孕酮都被认为通过其各自的细胞受体（ERα和ERβ，包括剪接变体ERβ2、AR和PGR）与免疫系统相互作用。在这项研究中，使用标准手动qPCR或qPCR阵列（TLDA）分析外周血单核细胞（PBMC）和细胞亚群（CD 4+和CD 8 + T细胞，CD 56 + NK细胞，CD 14+单核细胞和CD 19 + B细胞）中SHR基因的表达水平。对9名健康个体包括男性（n = 2）、绝经前（Pre-MP，n = 5）和绝经后（post-MP，n = 2）女性进行PBMC取样，使用FACS将PBMC分离成细胞亚群。在月经周期的不同阶段，对10名MP前妇女的总PBMC进行纵向采样。我们发现ERα最丰富，并且出乎意料地，ERβ2是几个FACS分选的细胞亚群中的主要ERβ变体。在总PBMCs中，SHR（ERα、ERβ1、ERβ2和AR）的表达不随月经周期的不同而波动，PGR不表达。然而，一些免疫应答基因（GATA 3、IFNG、IL 1B、LTA、NFKB 1、PDCD 1、STAT 3、STAT 5A、TBX 21、TGFB 1、TNFA）在排卵期和黄体中期表达更多。性激素水平与SHR基因表达及免疫反应基因表达无明显相关性，但与雌激素受体β1基因表达呈正相关。这项研究为ER在免疫细胞中的分布提供了新的见解。此外，几种免疫反应基因的表达模式在月经周期的不同阶段之间存在显着差异，支持性激素在免疫反应中的作用。
Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.