title: IL-22 is rapidly induced by Pathogen Recognition Receptors Stimulation in Bone-Marrow-derived Dendritic Cells in the Absence of IL-23.
abstract: In vertebrates, microorganisms are recognized by pathogen recognition receptors (PRRs). Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of genes. Within these genes, the cytokines family plays a crucial function because of its role in adaptive immunity induction and in tissue-specific functional regulation, such as tissue repair and tissue homeostasis during steady state conditions. Within the myeloid compartment, dendritic cells (DCs) release a variety of inflammatory cytokines in response to microbes. In this study, we show that BMDCs release IL-22 directly upon PRRs activation without the need of IL-23 signaling as reported for other IL22-producing cells. Moreover, we demonstrate that cytokine IL-22 is rapidly released in a cell-specific manner as macrophages are not able to produce IL-22 through the same PRRs system. In addition, we characterize the intracellular signaling cascade required for IL-22 release in BMDCs. Myd88, MEK1/2, NFkb and AhR, but not p38, NFAT, and RORgt, were found to be involved in IL-22 regulation in DCs. Our study suggests that BMDCs possess a unique intracellular molecular plasticity which, once activated, directs different BMDCs functions in a cell-specific manner.
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fumagalli
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Torri
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Papagna
authors.affiliation: Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Citterio
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mainoldi
authors.affiliation: School of Medicine and Surgery, University of Milano-Bicocca, Milan, 20126, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Foti