Structure and biological functions of IL-31 and IL-31 receptors

Division of Medical Cell Biology, College of Life Sciences, Sichuan University, Chengdu, PR China.
Cytokine & growth factor reviews (Impact Factor: 6.54). 11/2008; 19(5-6):347-56. DOI: 10.1016/j.cytogfr.2008.08.003
Source: PubMed

ABSTRACT Interleukin-31, produced mainly by activated CD4(+) T cells, is a newly discovered member of the gp130/IL-6 cytokine family. Unlike all the other family members, IL-31 does not engage gp130. Its receptor heterodimer consists of a unique gp130-like receptor chain IL-31RA, and the receptor subunit OSMRbeta that is shared with another family member oncostatin M (OSM). Binding of IL-31 to its receptor activates Jak/STAT, PI3K/AKT and MAPK pathways. IL-31 acts on a broad range of immune- and non-immune cells and therefore possesses potential pleiotropic physiological functions, including regulating hematopoiesis and immune response, causing inflammatory bowel disease, airway hypersensitivity and dermatitis. This review summarizes the recent findings on the biological characterization and physiological roles of IL-31 and its receptors.

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    • "Recent studies have shown that IL-31RA forms a functional receptor complex for IL-31 together with the beta subunit of oncostatin M receptor (OSMRß). IL-31 might be involved in controlling keratinocyte differentiation and proliferation and also has a number of effects that point to a role in the regulation of immune responses in skin [8] [11]. "
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    ABSTRACT: Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.
    BioMed Research International 06/2014; 2014:653724. DOI:10.1155/2014/653724 · 2.71 Impact Factor
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    • "Several studies have reported associations with SCS/CM with genetic markers on chromosome 20 (Sodeland et al., 2011; Meredith et al., 2012; Sahana et al., 2013) with many of them overlapping or nearby the regions detected in this study. Nevertheless, a number of possible candidate genes have been identified including the IL31Rα gene which acts as part of a receptor complex for the IL-31 cytokine in the activation of signaling pathways including the JAK-STAT and MAPK pathways which can initiate a wide range of immunological processes (Zhang et al., 2008; Cornelissen et al., 2012). The detection of a QTL region in close proximity to a number of genes of the complement system also looks promising given the importance of the complement system in both host innate and adaptive immunity. "
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    ABSTRACT: Mastitis is an inflammation-driven disease of the bovine mammary gland that occurs in response to physical damage or infection and is one of the most costly production-related diseases in the dairy industry worldwide. We performed a genome-wide association study (GWAS) to identify genetic loci associated with somatic cell score (SCS), an indicator trait of mammary gland inflammation. A total of 702 Holstein-Friesian bulls were genotyped for 777,962 single nucleotide polymorphisms (SNPs) and associated with SCS phenotypes. The SCS phenotypes were expressed as daughter yield deviations (DYD) based on a large number of progeny performance records. A total of 138 SNPs on 15 different chromosomes reached genome-wide significance (corrected p-value ≤ 0.05) for association with SCS (after correction for multiple testing). We defined 28 distinct QTL regions and a number of candidate genes located in these QTL regions were identified. The most significant association (p-value = 1.70 × 10−7) was observed on chromosome 6. This QTL had no known genes annotated within it, however, the Ensembl Genome Browser predicted the presence of a small non-coding RNA (a Y RNA gene) in this genomic region. This Y RNA gene was 99% identical to human RNY4. Y RNAs are a rare type of non-coding RNA that were originally discovered due to their association with the autoimmune disease, systemic lupus erythematosus. Examining small-RNA sequencing (RNAseq) data being generated by us in multiple different mastitis-pathogen challenged cell-types has revealed that this Y RNA is expressed (but not differentially expressed) in these cells. Other QTL regions identified in this study also encoded strong candidate genes for mastitis susceptibility. A QTL region on chromosome 13, for example, was found to contain a cluster of β-defensin genes, a gene family with known roles in innate immunity. Due to the increased SNP density, this study also refined the boundaries for several known QTL for SCS and mastitis.
    Frontiers in Genetics 11/2013; 4:229. DOI:10.3389/fgene.2013.00229
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    • "IL6-type cytokines are a family of cytokines including IL6, IL11, LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT1) and cardiotrophin-like cytokine (CLC) (Heinrich et al., 2003). Two newly discovered cytokines have recently been added to this family: IL31 and IL27 (Dillon et al., 2004; Zhang et al., 2008). IL6 family cytokines characteristically have both pro-and anti-inflammatory properties, and members are all major players in the regulation of the acute phase response and immune response (Heinrich et al., 2003). "
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    ABSTRACT: IL6 is a multifunctional cytokine with pivotal roles in the inflammatory response and in directing T cell differentiation in adaptive immunity. IL6 is widely expressed in the female reproductive tract and gestational tissues, and exerts regulatory functions in embryo implantation and placental development, as well as the immune adaptations required to tolerate pregnancy. Here, we summarise the current understanding of how membrane-bound and soluble receptors mediate IL6 signalling to regulate leukocytes and non-haemopoietic cells. We review the published literature regarding the expression and actions of IL6 in the uterus, decidua and placenta, and studies implicating this cytokine in pregnancy disorders. Elevated IL6 is frequently evident in the altered cytokine profiles characteristic of unexplained infertility, recurrent miscarriage, preeclampsia and preterm delivery. Notably, there is compelling evidence indicating altered systemic IL6 trans-signalling in women prone to recurrent miscarriage, with excessive IL6 bioavailability potentially inhibiting generation of CD4+ T regulatory cells required for pregnancy tolerance. Insufficient local IL6 may also contribute to fetal loss, since IL6 expression is reduced in the endometrium of women with recurrent miscarriage, and in the fetal-placental tissue of CBA×DBA/2 mice. Consistent with the role of IL6 in key reproductive events, Il6 null mutant mice exhibit elevated fetal resorption and delayed parturition. Investigation of the association between IL6 signalling components and T cell responses in pregnant women, as well as detailed analysis of the maternal immune response in IL6-deficient mice, is now required to define the mechanisms by which this cytokine exerts influence on reproductive success.
    Journal of Reproductive Immunology 07/2012; 95(1-2):1-14. DOI:10.1016/j.jri.2012.05.004 · 2.37 Impact Factor
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