title: 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.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kunz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Doecke
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Khusru
authors.initials: K
authors.lastname: Asadullah
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000099180:Interleukin-24
chemical_list: D016753:Interleukin-10; D053709:Interleukin-10 Receptor alpha Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000099180:Interleukin-24; C508609:IL10 protein, human; C421250:IL19 protein, human; C498891:Il19 protein, mouse; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C492510:interleukin-20 receptor; C415369:interleukin-22 receptor; C422042:interleukin 20