Interleukin 22 (IL-22) is mainly produced by activated Th1 cells. The data presented here indicate that neither resting nor activated immune cells express IL-22 receptor, and IL-22 did not have any effects on these cells in vitro and in vivo. In contrast, cells of the skin and the digestive and respiratory systems represent putative targets of this cytokine. The expression of IL-22 receptor in keratinocytes was upregulated by Interferon-gamma. In these cells, IL-22 activated STAT3 and directly and transcriptionally increased the expression of beta-Defensin 2 and beta-Defensin 3. High levels of IL-22 were associated with strongly upregulated beta-Defensin expression in skin from patients with T cell-mediated dermatoses. Taken together, IL-22 does not serve the communication between immune cells but is a T cell mediator that directly promotes the innate, nonspecific immunity of tissues.

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‐γ, 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‐γ 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 up‐regulated 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 anti‐psoriatic therapy. In summary, despite similarities, IFN‐γ primarily amplifies inflammation, while IL‐22 may be important in the innate immunity and reorganization of epithelia.

No abstract

This study investigated the expression of five novel human IL-10-related molecules and their receptors in blood mononuclear cells. IL-19 and IL-20 were found to be preferentially expressed in monocytes. IL-22 and IL-26 (AK155) expression was exclusively detected in T cells, especially upon type 1 polarization, and in NK cells. IL-24 (melanoma differentiation-associated gene 7) expression was restricted to monocytes and T cells. Detection of these molecules in lymphocytes was predominantly linked to cellular activation. Regarding T cells, IL-26 was primarily produced by memory cells, and its expression was independent on costimulation. In contrast to the high expression of receptors for IL-10 homologs in different tissues and cell lines, monocytes and NK, B, and T cells showed clear expression only of IL-10R1, IL-10R2, and IL-20R2. In these cells, IL-20R2 might be part of a still-unknown receptor complex. Therefore, immune cells may represent a major source but a minor target of the novel IL-10 family members.

Interleukin-22 (IL-22) is a key effector molecule that is produced by activated T cells, including T helper 22 (TH22) cells, TH17 cells and TH1 cells, as well as subsets of innate lymphoid cells. Although IL-22 can act synergistically with IL-17 or tumour necrosis factor, some important functions of IL-22 are unique to this cytokine. Data obtained over the past few years indicate that the IL-22-IL-22 receptor subunit 1 (IL-22R1) system has a high potential clinical relevance in psoriasis, ulcerative colitis, graft-versus-host disease, certain infections and tumours, as well as in liver and pancreas damage. This Review highlights current knowledge of the biology of the IL-22-IL-22R1 system, its role in inflammation, tissue protection, regeneration and antimicrobial defence, as well as the positive and potentially negative consequences of its therapeutic modulation.