441 Cell type specific expression and induction of IL-33 mRNA and protein

Abstract

Key mediators of innate immunity during skin inflammation are cytokines of the interleukin-1 (IL-1) family. While IL-1α and IL-18 are well characterized and are activated via inflammasome activation, the activation of IL-33 is still cryptic and in contrast, IL-33 is claimed to be inactivated by caspases. Recent data suggest that IL-33 acts as an alarm or danger signal and is released after cell damage. Besides binding to its specific receptor ST2, IL-33 can be present in the nucleus and in the cytosol. Here, we aim to elucidate the induction of IL-33 and its receptor ST2 compared to the other IL-1 family members IL-1α and IL-1β in different cell types and studied the cellular localization of the alarmin IL-33. We analyzed human and murine myeloid cells and epithelial cells and tested the expression of IL-33 mRNA and protein after stimulation of different pattern recognition receptors. The cellular localization of IL-33 was identified by Western blotting of nuclear and cytosolic cell extracts and by immunofluorescence. Interestingly, we found very different expression levels of IL-33 in certain myeloid cells and tissue-resident cells in both human and mice. High baseline levels of IL-33 were even present in cells that do not carry an inflammasome and are not able to activate inflammatory caspases. In analogy to IL-1α and IL-1β, IL-33 can be induced in myeloid cells by certain stimuli and signaling pathways. However, expression levels and kinetics of IL-33 seem to be different from IL-1α and IL-1β. In conclusion, we demonstrate a different activation pattern of IL-1α, IL-1β and IL-33 in myeloid and non-myeloid cells. As all these innate mediators are released during cutaneous damage we hypothesize that the activation of inflammasomes or inflammatory caspases influences not only the innate immune response but also the adaptive immune response in very early stages of skin inflammation.