Interleukin 31
IL31 | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl |
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UniProt |
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RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) | Chr 12: 122.17 – 122.17 Mb | n/a | |||||||
PubMed search | [2] | n/a |
View/Edit Human |
Interleukin-31 (IL-31) is a
IL-31 is produced by a variety of cells, namely type 2 helper (
Structure
IL-31 is a cytokine with an anti-parallel four-helix bundle structure in the gp130/IL-6 cytokine family.[5] This family includes IL-6, IL-11, IL-27, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), and neuropoietin (NP).[6] The anti-parallel bundles that these proteins form have an "up-up-down-down" topology, which is a relevant structure regarding the cytokine binding to their respective receptor complex.[5] The cytokines in the IL-6 family signal through type I cytokine receptors. Type I cytokine receptors are defined by sharing their cytokine binding domain (CBD) with conserved cysteine residues and a conserved WSxWS motif in the extracellular domain.[5] The receptors form heteromeric complexes that usually contain the glycoprotein 130 (gp130), which is important for activating downstream signaling pathways.[5] IL-31 is unique in this family of cytokines because its receptor complex does not contain gp130. The receptor for IL-31 is a heterodimer of the interleukin 31 receptor alpha (IL-31RA) and OSMR.[5] IL-31RA was originally referred to as GLM-R (for gp130-like monocyte receptor) or GPL (for gp130-like receptor).[5] Although the IL-31 receptor complex lacks gp130, IL-31RA has similarities to gp130 like its previous descriptors suggest.
Signaling
IL-31 signals via a receptor complex that is composed of IL-31 receptor A (
Function
Interleukin 31 is an
IL-31 and its receptors are also involved in regulating
Clinical significance
IL-31 is believed to play a role in chronic inflammation diseases.[4][7] One of these diseases is atopic dermatitis, or eczema. When biopsy samples of patients with atopic dermatitis were compared to samples from patients without atopic dermatitis, levels of IL-31 were elevated in patients with atopic dermatitis. IL-31 plays a role in this disease by inducing chemokine genes CCL1, CCL17, and CCL22.[6] The chemokines transcribed from these genes recruit T-cells to the irritated skin where they secrete more IL-31. This cycle is the current understanding of IL-31's role in atopic dermatitis. Along with atopic dermatitis, IL-31 is believed to play a role in inflammatory bowel disease and airway hypersensitivity.[6]
Pruritic forms of inflammatory skin diseases, or itchy skin diseases, have been found to have elevated levels of IL-31 mRNA in patient biopsies.[6] Analysis of the tissue distribution of the IL-31 receptor complex found that IL-31RA is abundant in dorsal root ganglia of different human tissues.[6] Dorsal root ganglia is where the cell bodies of primary sensory neurons reside. Dorsal root ganglia are also believed to be where the "itch" sensation originates.[6] These findings support the elevated levels of IL-31 in skin biopsies of pruritic skin diseases.
A monoclonal antibody against IL-31 named Lokivetmab is available for the treatment of canine atopic dermatitis.[9]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000204671 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: interleukin 31".
- ^ S2CID 12442845.
- ^ PMID 21982586.
- ^ PMID 18926762.
- ^ S2CID 21935134.
- PMID 26198770.