Staphylococcus aureus‐derived factors promote human Th9 cell polarization and enhance a transcriptional program associated with allergic inflammation. Issue 3 (17th January 2023)

• Record Type: Journal Article
• Authors: Badolati, Isabella; van der Heiden, Marieke; Brodin, David; Zuurveld, Marit; Szilágyi, Szilvia; Björkander, Sophia; Sverremark‐Ekström, Eva
• Is Part Of: European journal of immunology. Volume 53:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-17
• Subjects: allergy -- environmental stimuli -- retinoic acid -- Staphylococcus aureus -- T helper 9 cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202250083
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: T helper (Th) 9 cells, characterized by robust secretion of IL‐9, have been increasingly associated with allergic diseases. However, whether 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 the transcriptional level, such as FOXO1, miR‐155, and TNFRSF4. The 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. Abstract : The effects of environmental stimuli on Th9 cell polarization are largely unknown. Using several different in vitro approaches, we found that Staphylococcus (S.) aureus ‐derived factors strongly promote human Th9 cell polarization, while retinoic acid is able to dampen such effect and downregulates the S. aureus ‐induced Th9‐ and allergy‐associated genes.