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.

Stanniocalcin 2 Ameliorates Hepatosteatosis Through Activation of STAT3 Signaling

“…Here, in our studies we found that plasma IL-22 contents were reduced by STC2 treatment or overexpression ( Supplementary Figures S3A,B ). Previous studies have shown that inflammatory signaling, including NF-κB and AP-1/JunD, are involved in IL-22 production ( Ouyang et al, 2011 ; Ahlfors et al, 2014 ; Fumagalli et al, 2016 ). Since STC2 treatment can reduce hepatic inflammation in obese mice, we speculate that reduction of IL-22 in STC-2 treated mice might be attributed to decreased inflammation.…”

Nanoparticle-Based Cpg-Oligonucleotide Therapy For Treating Allergic Asthma

“…Although not investigated by Kline et al, subsequent independent studies in different allergy models suggested a role for IL-10 in CpG-ODN-mediated suppression of allergic Th2 responses [38]. Another potential mediator of CpG-ODN-induced suppression is the more recently discovered and enigmatic cytokine, IL-22, which can be upregulated in expression in DCs upon stimulation with CpG-ODN [39]. In separate studies, IL-22 has been shown to both promote and abrogate symptoms of allergic asthma, and it has been suggested that these apparently paradoxical roles may depend on the presence or absence of IL-17, respectively [40].…”

Interleukin-22 Influences the Th1/Th17 Axis

“…The IL-23 receptor has been detected on Th17 cells, natural killer T (NKT) cells, type 3 innate lymphoid cells (ILC3), gamma delta (γδ) T cells, macrophages, dendritic cells (DC), and neutrophils. Stimulation of these cells with IL-23 can induce production of IL-22 ( 11 , 18 , 29 , 31 , 32 , 37 , 38 ). Moreover, IL-1β can act both independently of and synergistically with IL-23 to induce IL-22 ( 18 , 37 , 39 ).…”