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Application: Screen and characterize modulators of IL-31 activity.Screen anti-IL-31 and anti-IL-31RA antibodies.
Background: IL-31 (interleukin 31) is a four-helix bundle proinflammatory cytokine preferentially produced by T helper type 2 (TH2) cells. IL-31 regulates cell differentiation, cell proliferation, and immune responses, serving as a neuroimmune link between TH2 cells and sensory neurons in generating a T cell-mediated inflammatory itch. The IL-31 receptor complex, composed of IL-31RA and OSMR (human oncostatin M receptor beta), is expressed by various epithelial and immune cells as well as dorsal root ganglia sensory neurons. IL-31 interacts with the IL-31 receptor complex, activating Janus kinases JAK1 and JAK2. This activation leads to the phosphorylation of signal transducer and activator of transcription (STAT) molecules, mainly STAT3, which upregulate the genes responsible for the IL-31 induced itch sensation. Often referred to as the itchy cytokine, increased expression of IL-31 or its receptor IL-31RA is correlated with alopecia, skin lesions, airway hypersensitivity, and particularly pruritic disorders such as atopic dermatitis. IL-31 and other TH2 related cytokines (including IL-4, IL-13 and TSLP (thymic stromal lymphopoietin) play an important role in the pathogenesis of a variety of inflammatory and allergic diseases and have become popular for therapeutic development. The IL-31RA targeting antibody Nemolizumab has been FDA-approved for the treatment of atopic dermatitis.
Description: IL-31 Responsive Luciferase Reporter HEK293 Cell Line was engineered to express the human IL-31 receptor complex, composed of human IL-31 receptor alpha (hIL-31RA [NM_139017.7]) and human oncostatin M receptor beta (hOSMR [NM_003999.3]) separated by a self-cleaving P2A peptide. The cell line was generated by lentiviral transduction of STAT3 Luciferase Reporter HEK293 cells (cat#79800-P) which express firefly luciferase driven by STAT3 response elements located upstream of a minimal TATA promoter. IL-31 activity can be monitored by measuring luciferase activity.The functionality of this cell line was validated as responding to human IL-31, and by showing that IL-31-induced luciferase activity can be inhibited by anti-IL31 neutralizing antibodies.Figure 1: Illustration of the mechanism of IL-31 Responsive Luciferase Reporter HEK293 Cell Line.IL-31 initially binds to IL-31RA and then to OSMR to form a high affinity receptor complex. This binding leads to phosphorylation of STAT3 via the associated JAK1/2 pathways. After phosphorylation, STAT3 is translocated to the nucleus where it induces the transcription of firefly luciferase after binding to the response elements.Interested in screening and profiling inhibitors or blocking antibodies in a cell culture assay without the need to purchase and license the cell line? Check out our Cell Signaling Pathway Screening.
Genbank: NM_003999.3
Host Cell Line: HEK293, Human Embryonic Kidney, epithelial-like cells, adherent
Mycoplasma Testing: The cell line has been screened to confirm the absence of Mycoplasma species.
Storage Stability: Cells are shipped in dry ice and should immediately be thawed or stored in liquid nitrogen upon receipt. Do not use a -80°C freezer for long term storage.
Supplied As: Each vial contains ≥1 x 106 cells in 1 ml of Cell Freezing Medium (BPS Bioscience #79796)
Target: IL-31
Uniprot: Q6EBC2
Warnings: Avoid freeze/thaw cycles.
Biosafety Level: BSL-2
References: Bağci I., et al., 2018 J Allergy and Clin Immunol. 141(3): 858-866.Datsi A., et al., 2021 Euro J Allergy and Clin Immunol. 76(10): 2982-2997.Dillon S., et al., 2004 Nat. Immunol. 5(7): 752-760.Dubin C., et al., 2021 Expert Rev Clin Immunol. 17(8): 835-852.Nemmer J., et al., 2021 Front. Med. 8: 639097.Takahashi S., et al., 2023 Cell Rep. 42(12): 113433
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