IL-22 Promotes Fibroblast-Mediated Wound Repair in the Skin (original) (raw)
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IL‐22 in tissue‐protective therapy
British Journal of Pharmacology, 2013
IL‐22, a member of the IL‐10 cytokine family, has recently gained significant attention as a protective agent in murine models of diseases driven by epithelial injury. Like its biochemical and functional sibling IL‐10, IL‐22 elicits cellular activation primarily by engaging the STAT3 signalling pathway. Exclusively produced by leukocytes, but targeting mostly cells of epithelial origin, IL‐22 has been proposed as a specialized cytokine messenger acting between leukocytic and non‐leukocytic cell compartments. A lack of response in leukocytes to IL‐22 mirrors tightly controlled IL‐22 receptor expression and probably explains the apparent lack of instant adverse effects after systemic IL‐22 administration to mice. Anti‐apoptotic, pro‐proliferative and pro‐regenerative characteristics the major biological properties of this cytokine. Specifically, application of IL‐22 is associated with tissue protection and/or regeneration in murine models of infection/microbe‐driven inflammation at ho...
Dermatology
Twenty years after the cloning, characterization, and identification of interleukin (IL)-22 in 2000, the precise biological role of this cytokine in healthy and unhealthy skin is not completely known. The aim of this review is to provide an overview on the recent knowledge available in literature about the origin, sources, targets, molecular mechanism of action, and clinical issues regarding IL-22. Last but not least, recent experimental evidence obtained in a 3D model of organotypic culture of normal human skin highlights its homeostatic role and will be discussed in detail, as personal observations. As most of the data concerning IL-22 immunomodulating activity are obtained from mouse models, this work offers a new perspective on its clinical role. The hypothesis herein advanced is that IL-22 profoundly affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.
Contributions of IL-22 to TH17 Responses: Repairing and Protecting Peripheral Tissues
IL-17, IL-22 and Their Producing Cells: Role in Inflammation and Autoimmunity, 2012
IL-22 is a cytokine mainly produced by Th17 cells under the control of IL-23. Although this cytokine is structurally related to IL-10, it does not share any activity with IL-10 and is, so far, completely devoid of activity on immune and hematopoietic cells. IL-22 responsive cells are mainly found in peripheral tissues and include keratinocytes, lung and intestinal epithelial cells as well as hepatocytes. In vivo, IL-22 expression fits with the spectrum of inflammatory processes related to Th17 activation, including multiple sclerosis, inflammatory bowel disease and psoriasis in human. However, its pathophysiological significance varies in each of these diseases. IL-22 does not seem to play any major role in multiple sclerosis, at least based on the classical mouse model for this disease. By contrast, this cytokine appears to play a protective role in mucosal inflammation both in lungs and colon. Finally, IL-22 turns out to be one of the main proinflammatory mediators responsible for inappropriate activation of keratinocytes in psoriasis lesions, raising some promising perspectives for future clinical applications.
The role of IL-22 in the resolution of sterile and nonsterile inflammation
Clinical & Translational Immunology
In a broad sense, inflammation can be conveniently characterised by two phases: the first phase, which is a pro-inflammatory, has evolved to clear infection and/or injured tissue; and the second phase concerns regeneration of normal tissue and restitution of normal physiology. Innate immune cell-derived pro-inflammatory cytokines and chemokines activate and recruit nonresident immune cells to the site of infection, thereby amplifying the inflammatory responses to clear infection or injury. This phase is followed by a cytokine milieu that promotes tissue regeneration. There is no absolute temporal distinction between these two phases, and cytokines may have dual pleiotropic effects depending on the timing of release, inflammatory microenvironment or concentrations. IL-22 is a cytokine with reported pro-and antiinflammatory roles; in this review, we contend that this protein has primarily a function in restitution of normal tissue and physiology.
IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice
PloS one, 2017
Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PD...
European Journal of Immunology, 2006
IL-22 is an IFN-IL-10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL-22, in contrast to its relative IFN-c, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL-22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN-c favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL-22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL-22 effects. IL-22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL-22 levels in psoriatic skin were associated with strongly upregulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL-22 plasma levels, which correlated with the disease severity. Expression of IL-22 and IL-22-regulated genes was reduced by antipsoriatic therapy. In summary, despite similarities, IFN-c primarily amplifies inflammation, while IL-22 may be important in the innate immunity and reorganization of epithelia.