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Due to their structural similarity, interleukin (IL)-19, IL-20, IL-22, IL-24 and IL-26 were combined with IL-10 in the so-called IL-10 family. To expand the knowledge on IL-19, IL-20 and IL-24, we systematically and quantitatively analysed the expression of these mediators and their receptor chains in vitro and in vivo under various conditions and in comparison with other IL-10 family members. In vitro, IL-19, IL-20 and IL-24 were produced not only by activated immune cells, particularly monocytes, but also to a similar extent by keratinocytes. IL-1 β increased the expression of these mediators 1000-fold (IL-19) and 10-fold (IL-20 and IL-24) in keratinocytes. In vivo, these cytokines were expressed preferentially in inflamed tissues. The absence of either R1 chain for the two types of receptor complexes for these cytokines (IL-20R1/IL-20R2 and IL-22R1/IL-20R2) on immune cells implies that they cannot act on these cells. In fact, IL-19, IL-20 and IL-24 did not induce activation of signal transducer and activator of transcription (STAT) molecules in immune cells. Instead, several tissues, particularly the skin, tissues from the reproductive and respiratory systems, and various glands appeared to be the main targets of these mediators. Keratinocytes expressed both receptor complexes; however, the expression of IL-22R1 was 10 times higher than that of IL-20R1. Interferon- γ further increased the expression of IL-22R1 and decreased that of IL-20R1, suggesting that under T1 cytokine conditions these mediators primarily affect keratinocytes via the IL-22R1/IL-20R2 complex. In summary, these data support the notion that IL-19, IL-20 and IL-24 are distinct from classical ILs and constitute a separate subfamily of mediators within the IL-10 family. [ABSTRACT FROM AUTHOR]

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-γ. In these cells, IL-22 activated STAT3 and directly and transcriptionally increased the expression of β-Defensin 2 and β-Defensin 3. High levels of IL-22 were associated with strongly upregulated β-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. [Copyright &y& Elsevier]