IL-31: A new link between T cells and pruritus in atopic skin inflammation

Sonkoly, Enikö; Müller, Anja; Lauerma, Antti; Pivarcsi, Andor; Soto, Hortensia; Kemény, Lajos; Alenius, Harri; Dieu-Nosjean, Marie Caroline; Meller, Stephan; Rieker, Juliane; Steinhoff, Martin; Hoffmann, Thomas; Ruzicka, Thomas; Zlotnik, Albert; Homey, Bernhard

doi:10.1016/j.jaci.2005.10.033

Cited by 861 publications

(777 citation statements)

References 35 publications

(47 reference statements)

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“…The transcripts and protein levels of IL-31 and the number of Th2 cells that secrete IL-31 are elevated in various skin diseases including atopic dermatitis, atopic contact dermatitis, and purigo nodularis (7)(8)(9). IL-31 is thought to play an important role in the induction of pruritus, which is a characteristic feature of these skin diseases (10).…”

Section: Interleukin 31 Receptor ␣ (Il-mentioning

confidence: 99%

Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression

Edukulla

Singh

Jegga

et al. 2015

Journal of Biological Chemistry

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Background: IL-31RA is a novel Type I cytokine receptor that pairs with oncostatin M receptor to mediate IL-31 signaling. Results: Th2 cytokines up-regulate IL-31RA signaling in macrophages. Conclusion: We demonstrate that the Th2 cytokines IL-4 and IL-13 were capable of up-regulating IL-31RA expression on macrophages. Significance: This newly identified counter-regulatory role between Th2 cytokine and the IL-31 signaling cascade may provide valuable insights into the pathobiology of allergic diseases.

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Section: Interleukin 31 Receptor ␣ (Il-mentioning

confidence: 99%

Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression

Edukulla

Singh

Jegga

et al. 2015

Journal of Biological Chemistry

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“…The receptor of IL-31 consists of IL-31 receptor A (IL-31RA) and the oncostatin M receptor that is constitutively expressed on epithelial cells (8). The role of IL-31 in allergic diseases mainly focused on atopic dermatitis.…”

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confidence: 99%

Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis

et al. 2014

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Background: Interleukin-31 (IL-31) is a recently described cytokine that is involved in helper T cell type-2 (Th2)-mediated diseases. However, its regulatory effect in the pathogenesis of children allergic rhinitis (AR) needs to be further characterized. This study sought to evaluate the expression and role of IL-31 in children with AR. Methods: Sixty children with AR and 20 normal controls were included. IL-31 and Th2 cytokines production in tissue, serum, and nasal lavage was examined by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay, respectively. Peripheral blood mononuclear cells (PBMCs) were purified for in vitro regulation experiment of IL-31. Nasal epithelial cells (NECs) were cultured and stimulated by recombinant IL-31. results: The IL-31 mRNA and protein levels in both serum and nasal lavage were significantly enhanced in AR compared with normal controls, especially in children with asthma. The nasal IL-31 was associated with enhanced local Th2 cytokines and mucin 5AC (MUC5AC) expression. In vitro study showed that IL-31 promotes Th2 cytokines expression and MUC5AC upregulation and thus amplified Th2 inflammation. conclusion: Our results demonstrate that IL-31 expression in AR aggravated and amplified Th2 inflammation as well as mucin production, and provide a possible explanation for IL-31's regulatory role in the pathogenesis of AR. a llergic rhinitis (AR) is a common nasal disease and affects 10-40% of children with increasing prevalence (1,2). AR frequently coexists with asthma (most studies report a rate of 50-60%) in children (3). The major histological features of AR include helper T cell type-2 (Th2) inflammation accompanied by infiltration with eosinophils, allergen-specific IgE production, and thickening of the basement membrane (4,5). Activation of Th2 cells and further released cytokines induced accumulation of inflammatory cells, such as B cells, plasma cells, eosinophils, basophils, and neutrophils, which contributed to the occurrence of AR (6). Despite involvement of Th2 inflammation in AR was clearly clarified, its regulation was not fully understood.Interleukin-31 (IL-31) is a newly discovered four-helix bundle cytokine and expressed by several types of cells under both normal and disease state, such as activated CD4 + T cells, mast cells, monocytes, macrophages, immature and mature monocyte-derived dendritic cells and so on (7). The receptor of IL-31 consists of IL-31 receptor A (IL-31RA) and the oncostatin M receptor that is constitutively expressed on epithelial cells (8). The role of IL-31 in allergic diseases mainly focused on atopic dermatitis. Stephan et al. reported elevated IL-31 expression in atopic dermatitis (9). UIrike et al. found a correlation of Th2 cytokines with increased level of IL-31 in children with extrinsic atopic dermatitis (10). However, studies on respiratory allergic diseases are relatively few. Recently, Lei et al. (11) reported that high IL-31 level in asthmatic subjects, suggesting that IL-31 ...

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“…14) as a member of the IL-6R group that does not engage gp130, but OSMR␤, to form a signaling receptor complex (15,16). Based on the effects of ectopic expression in transgenic mice, IL-31, a CD4 ϩ T-cell-derived cytokine, has been associated with pruritis and dermatitis affecting dermal keratinocytes and dorsal root ganglia (17)(18)(19). Because antigenic challenge increased levels of IL-31 in a mouse model of airway hyper-responsiveness, this cytokine has also been proposed to play a role in airway hypersensitivity (15).…”

mentioning

confidence: 99%

“…Considering the limitations of transient expression systems, the precise function of the IL-31R complex beyond the immediate signaling reactions and quantitative comparison to the action by the other IL-6 cytokine receptors remains to be determined. Despite the prediction of IL-31-responsive epidermal keratinocytes and other epithelial cells (15,(17)(18)(19), the study of the receptor signaling in these cells proved to be challenging because the level of IL-31R␣ is low relative to that of OSMR␤.…”

mentioning

confidence: 99%

Interleukin-31 and Oncostatin-M Mediate Distinct Signaling Reactions and Response Patterns in Lung Epithelial Cells

Chattopadhyay

Tracy

Liang

et al. 2007

Journal of Biological Chemistry

121

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Many mammalian cell types co-express several receptors for the evolutionarily related hematopoietic cytokines of the interleukin (IL) 4 -6 group (1). Moreover, all cell types express gp130, the common signal-transducing subunit of this receptor family. A major unresolved issue is whether the receptors for the individual IL-6 cytokines exert redundant functions because of the involvement of shared subunits, or whether they exert specific actions because of the formation of heteromeric subunit combinations. Gross analyses of cell responses to IL-6 cytokines indicated similar signaling reactions, supporting the notion of redundancy (2, 3). However, the individual receptor forms determine not only the ability of the cells to respond to specific IL-6 cytokines by mediating ligand binding but also the quantitative signaling by the relative expression levels of receptor subunits (4). The model of IL-6 cytokine receptors directing specific action takes into consideration that receptor complexes engage cytoplasmic domains of two signal-transducing subunits with distinct structures and capabilities to communicate to signaling pathways (3, 5). The ligand-dependent association of receptor subunits into signaling-competent complexes leads invariably to the activation of JAKs and to a specific pattern of auto-and trans-tyrosine phosphorylation of kinases, receptor subunits, and interacting proteins, including STATs, Src homology 2-containing phosphatase 2, Src homology 2-containing protein C (SHC) and other adaptor proteins. The receptor proximal events at the plasma membrane and the level of sustained signaling defines the duration and magnitude of cell responses, including transcriptional induction of genes, altered cell morphology, and changes in cell proliferation. Proliferation control by cytokine-activated STAT proteins has gained particular attention in part to explain the role of IL-6 cytokines in tissue damage repair (6 -8) and potential relevance to support tumorigenesis (9, 10). Unexplained thus far is the basis for the divergent outcome of IL-6 cytokine action that, in certain epithelial cell types, yields a suppression of proliferation (11), whereas in other cell types it yields a growth promotion (12, 13). Because the subunits for IL-6 cytokine receptors are encoded by single-copy genes, comparable structures and biochemical actions are expected for the receptor proteins expressed in the various cell types, regardless of the ultimate outcome of cytokine treatment.An independent assessment of receptor signaling specificity among IL-6 cytokine receptors became possible with the identification of IL-31R␣ (gp130-like protein; see Ref. 14) as a member of the IL-6R group that does not engage gp130, but OSMR␤, to form a signaling receptor complex (15,16). Based on the effects of ectopic expression in transgenic mice, IL-31, a CD4 ϩ T-cell-derived cytokine, has been associated with pruritis and dermatitis affecting dermal keratinocytes and dorsal root ganglia (17-19). Because antigenic challenge increased levels of * Th...

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IL-31: A new link between T cells and pruritus in atopic skin inflammation

Cited by 861 publications

References 35 publications

Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression

Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression

Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis

Interleukin-31 and Oncostatin-M Mediate Distinct Signaling Reactions and Response Patterns in Lung Epithelial Cells

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