Interleukin (IL)‐19, IL‐20 and IL‐24 are produced by and act on keratinocytes and are distinct from classical ILs

Abstract

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-1beta 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-gamma 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.

Deficiency of IL-22 Contributes to a Chronic Inflammatory Disease: Pathogenetic Mechanisms in Acne Inversa

“…In contrast to IL-22, IL-20 is mainly produced by keratinocytes (25,47,48), and IL-10 does not regulate the keratinocyte biology due to the lack of one of the IL-10 receptor subunits, IL-10R1 (Fig. 6E).…”

Long-range regulation of cytokine gene expression

“…Originally considered to be a Th2 cytokine, IL-10 can be produced by all types of CD4 effectors and by CD8 T cells, macrophages, and B, mast and dendritic cells (47,48). By contrast, IL-19, IL-20 and IL-24 are produced primarily by macrophages (49,50). A number of DNase HS sites have been identified within 30 kb of murine Il10, some of which can act as enhancers (50), but their role in the regulation of Il10, whether any act on neighboring genes, and the 3-dimensional architecture of this locus are unknown.…”

Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines

“…Transgenic (Tg) mice overexpressing IL-20 exhibit a phenotype similar to human psoriatic skin, and IL-20 neutralizing antibodies resolve psoriasis in a human xenograft transplation model (1,12). Increased levels of IL-19 and IL-24 are also observed in skin samples from psoriasis patients, but the significance and/or biological function of IL-19 and IL-24 is less clear (3). IL-24 Tg mice exhibit epidermal hyperplasia and proliferation, suggesting IL-24 activity in vivo is similar to IL-20 (13).…”