GSE162051
RNA-sequencing analysis of the effect of progesterone on T cell activation
The changes in progesterone (P4) levels during and after pregnancy coincide with the temporary improvement and worsening of several autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis (RA). Most likely immune-endocrine interactions play a major role in these pregnancy-induced effects. In this study, we used next generation sequencing to investigate the direct effects of P4 on CD4+ T cell activation, of central importance in pregnancy and disease. We found that P4 had a profound dampening effect on T cell activation, altering the gene and protein expression profile and reversing many of the changes induced during the activation. The transcriptomic changes induced by P4 were significantly enriched for genes associated with diseases known to be modulated during pregnancy such as MS, RA and psoriasis. The TH1-and TH17-associated transcription factors STAT1 and STAT3 were significantly downregulated by P4 and their downstream targets were significantly enriched among the diseases-associated genes. Several of these genes included well-known and disease-relevant cytokines, such as IL-12ß, CXCL10 and OSM, that were further validated also at the protein level using proximity extension assay. Our results extend the previous knowledge of P4 as an immune regulatory hormone and support its importance during pregnancy for regulating potentially detrimental immune responses towards the semi-allogenic fetus. Further, our results also point toward a potential role for P4 in the pregnancy-induced disease immunomodulation, suggestively through dampening of TH1 and TH17-associated immune responses and highlight the need for further studies evaluating P4 as a future treatment option. Overall design: Blood was collected in sodium-heparin tubes from healthy female controls (n=8). CD4+ T cells were isolated using positive immunomagnetic sorting and pre-incubated for 20 hrs with or without 50 uM of progesterone. Following pre-incubation, the cells were cultured unactivated or activated by plate-bound anti-CD3 and anti-CD28 antibodies in the presence or absence of 50 uM progesterone for 6 and 24 hrs.