Epithelial barrier integrity is of outermost importance to protect the human body from external harm. One of the key cytokines involved in tissue regeneration is interleukin (IL)-22. During inflammation, IL-22 producing cells are recruited into barrier organs to restore inflammation mediated barrier damage. The aryl hydrocarbon receptor (AhR) has been shown to regulate IL-22 expression in T cells. Previous results from our group indicated that another transcription factor Forkhead box O (FOXO) 4 is expressed in human T cells. FOXO4 has been mainly described as tumor suppressor and regulator of senescence and longevity. In line with this, FOXO4 mRNA is expressed in various tissues at low level and downregulated in most tumors. FOXO4 mRNA and protein have been detected in mouse CD4+ T cells and our group could assign FOXO4 expression to human T cells of the Th22 subset. To investigate the functional role of FOXO4 in T cells, lentiviral overexpression, and downregulation of FOXO4 in CD4+ effector T cells as well as in naïve T cells subsequently cultured under Th22 polarizing conditions, was performed. We show that FOXO4 and AhR regulate IL22 secretion in IL-6 and TNF-α induced Th22 cell cultures while in AhR-Agonist induced Th22 cultures IL-22 secretion is FOXO4 independent. A physiological role of FOXO4 dependent effects in IL-22 secretion was confirmed by scratch assays revealing decreased artificial wound healing with supernatants from FOXO4 deficient T cells. Here, we show that FOXO4 expression is induced and stabilized during in vitro differentiation of Th22 cells. Furthermore, we could describe FOXO4 as an important mediator for IL-22 expression in effector and differentiating naïve T cells in a pro-inflammatory induced setting.

ESDR344 - Foxo4 and AHR control inflammation-induced tissue damage via secretion of IL-22 in T cells

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.