Staphylococcus aureus-derived factors promote human Th9 cell polarization and enhance a transcriptional program associated with allergic inflammation.
Isabella BadolatiMarieke van der HeidenDavid BrodinMarit ZuurveldSzilvia SzilágyiSophia BjörkanderEva Sverremark-EkströmPublished in: European journal of immunology (2022)
T helper (Th) 9 cells, characterized by robust secretion of IL-9, have been increasingly associated with allergic disease. However, if and how Th9 cells are modulated by environmental stimuli remains poorly understood. In this study, we show that in vitro exposure of human PBMCs or isolated CD4 T-cells to Staphylococcus (S.) aureus-derived factors, including its toxins, potently enhances Th9 cell frequency and IL-9 secretion. Furthermore, as revealed by RNA sequencing analysis, S. aureus increases the expression of Th9-promoting factors at a transcriptional level, such as FOXO1, miR-155 and TNFRSF4. Addition of retinoic acid (RA) dampens the Th9 responses promoted by S. aureus and substantially changes the transcriptional program induced by this bacterium, while also altering the expression of genes associated with allergic inflammation. Together, our results demonstrate a strong influence of microbial and dietary factors on Th9 cell polarization, which may be important in the context of allergy development and treatment. This article is protected by copyright. All rights reserved.
Keyphrases
- single cell
- staphylococcus aureus
- induced apoptosis
- transcription factor
- endothelial cells
- gene expression
- oxidative stress
- cell therapy
- cell cycle arrest
- rheumatoid arthritis
- signaling pathway
- induced pluripotent stem cells
- long non coding rna
- quality improvement
- allergic rhinitis
- heat shock
- atopic dermatitis
- endoplasmic reticulum stress
- pseudomonas aeruginosa
- systemic lupus erythematosus
- bone marrow
- disease activity
- systemic sclerosis
- replacement therapy
- heat shock protein