期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 51, 期 10, 页码 2430-2440出版社
WILEY
DOI: 10.1002/eji.202049144
关键词
CD4(+) T cell activation; estrogen; human; progesterone; proteomics
类别
资金
- Swedish Foundation for Strategic Research [SB16-0011]
- Swedish Research Council [2018-02776]
- Swedish Lions Research Foundation
- Swedish Society of Medicine [SLS-879791]
- NEURO Sweden [F2018-0052]
- Swedish Foundation for MS Research
- Swedish Research Council [2018-02776] Funding Source: Swedish Research Council
- Swedish Foundation for Strategic Research (SSF) [SB16-0011] Funding Source: Swedish Foundation for Strategic Research (SSF)
The study found that estradiol can increase the activation and secretion of various immune- and inflammation-related proteins in T cells, while progesterone shows a biphasic pattern of effects on T cells at different concentrations, with its importance in immune modulation of T cells during pregnancy emphasized.
Estradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell-mediated diseases such as multiple sclerosis (MS). Although immune-endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2- and P4-mediated effects on human CD4(+) T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69/CD25 expression by flow cytometry, and secreted proteins (n = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy-relevant E2 concentrations increased activation and the secretion of several immune- and inflammation-related proteins. P4, on the other hand, showed a biphasic pattern, where serum-related concentrations upregulated activation and protein secretion while placenta-relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.
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