Cutting Edge: IL-26 Signals through a Novel Receptor Complex Composed of IL-20 Receptor 1 and IL-10 Receptor 2

Sheikh, Faruk; Baurin, Vitaliy V.; Lewis-Antes, Anita; Shah, Nital K.; Smirnov, Sergey V.; Anantha, Shubha; Dickensheets, Harold; Dumoutier, Laure; Renauld, Jean‐Christophe; Zdanov, Alexander; Donnelly, Raymond P.; Kotenko, Sergei V.

doi:10.4049/jimmunol.172.4.2006

Cited by 160 publications

(147 citation statements)

References 21 publications

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“…This receptor pair is not used by any other known ligand, although the CRF2-4 chain is also part of the IL-10, IL-22 and IL-26 receptors. [4][5][6][7] Binding of the IFN-l ligand to its receptor initiates signaling reminiscent of the Type-I interferons. In particular, STAT2 is phosphorylated, ISGF3 is activated and OAS and MxA are induced.…”

Section: Introductionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Section: Introductionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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“…IL-19 signals exclusively through the IL-20R1/ IL-20R2 heterodimer, whereas IL-20 and IL-24 can signal through IL-20R1/IL-20R2 as well as the IL-20R2 chain paired with IL-22R1 (11,(23)(24)(25). IL-22 signals through IL-22R1 paired with IL-10R2 (26,27), and IL-26 signals through a heterodimer composed of IL-20R1 and IL-10R2 (28,29). IL-20R1 and IL-20R2 are expressed in skin, lung, testis, and other tissues (11,17,28,29).…”

mentioning

confidence: 99%

“…IL-22 signals through IL-22R1 paired with IL-10R2 (26,27), and IL-26 signals through a heterodimer composed of IL-20R1 and IL-10R2 (28,29). IL-20R1 and IL-20R2 are expressed in skin, lung, testis, and other tissues (11,17,28,29). IL-22R1 is expressed by KCs, hepatocytes, and pancreatic acinar cells, as well as in the colon and the small intestine (13,17,26,27,30).…”

mentioning

confidence: 99%

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

Susan

Valdez²,

Wu³

et al. 2007

The Journal of Immunology

440

256

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IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasisassociated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, ␤-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.

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“…A typical feature of IL-26 is its high affinity for heparin that suggests similar affinity for glycosaminoglycans moieties on proteoglycans that could enrich the cytokine at the cell surface and work as IL-26 co-receptors. Enriched cytokines would bind to IL-20R1 and IL-10R2 receptors combination [139,140] and activate STAT1 and STAT3 transcription factors. This particular receptor combination is what gives IL-26 its specificity since the other IL-10 family members are not able to signal via this complex.…”

Section: Il-26mentioning

confidence: 99%

“…It is interesting to note that IL-26 is the only IL-10 family member that employs this pair of receptors in its function [13,[138][139][140]. However, little experimental data is currently available concerning crystal structures of IL-26 and its complexes with the cognate receptors.…”

Section: Considerations About Il-26 Binary and Ternary Complexesmentioning

confidence: 99%

Structure and function of interleukin-22 and other members of the interleukin-10 family

Trivella

Ferreira-Junior

Dumoutier

et al. 2010

Cell. Mol. Life Sci.

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The IL-10 family of cytokines is comprised of IL-10, . The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.

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Cutting Edge: IL-26 Signals through a Novel Receptor Complex Composed of IL-20 Receptor 1 and IL-10 Receptor 2

Cited by 160 publications

References 21 publications

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis

Structure and function of interleukin-22 and other members of the interleukin-10 family

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