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Canine interleukin-31 binds directly to OSMRβ with higher binding affinity than to IL-31RA

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Abstract

Interleukin-31 (IL-31) is a pro-inflammatory cytokine involved in skin inflammation and tumor progression. The IL-31 signaling cascade is initiated by its binding to two receptors, IL-31 receptor alpha (IL-31RA) and oncostatin M receptor subunit beta (OSMRβ). The previous study suggested that human IL-31 (hIL-31) directly interacts with IL-31RA and OSMRβ, independently, but the binding ability of hIL-31 to IL-31RA is stronger than to OSMRβ. In different to its human ortholog, feline IL-31 (fIL-31) has a higher binding affinity for feline OSMRβ. However, the binding pattern of canine IL-31 to its receptors remains to be elucidated. In this study, we purified the recombinant canine IL-31 (rcIL-31) protein and revealed its secondary structure to be mainly composed of alpha-helices. Moreover, in vitro studies show that rcIL-31 has the ability to induce the phosphorylation of signal transducer activator of transcription 3 (STAT3) and STAT5 in DH-82 cells. In the following, the binding efficacies of bioactive rcIL-31 for its individual receptor components have been measured using a flow cytometry assay. The result demonstrates that correctly refolded rcIL-31 binds independently with cIL-31RA and cOSMRβ which were expressed on the cell surface. Of note, rcIL-31 has a greater than tenfold higher affinity to OSMRβ than to IL-31RA. Additionally, we demonstrated that D1–D4, especially D4 of cOSMRβ, is crucial for its binding to cIL-31. Furthermore, this study proved that rcIL-31 has a high binding affinity to the soluble cOSMRβ with a KD value of 3.59 × 10–8 M. The results presented in the current study will have a significant implication in the development of drugs or antibodies against diseases induced by cIL-31 signaling.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work is supported by Tian** Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-KJGG-014 and TSBICIP-IJCP-001) and the National key research and development program of China (2020YFA0907104).

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  1. Yuxin Zheng and **g Zhang contributed equally.

Authors and Affiliations

  1. College of Biological Engineering, Tian** University of Science and Technology, Tian**, 300457, China

    Yuxin Zheng, ** Cao & Hua Sun

  2. Laboratory of Protein Engineering and Vaccines, Tian** Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tian**, 300308, China

    Yuxin Zheng, **g Zhang, Tianling Guo, ** Cao, Lixian Wang, Jie Zhang, Xuefei Pang, Feng Gao & Haixia **ao

  3. National Technology Innovation Center of Synthetic Biology, Tian**, 300308, China

    Yuxin Zheng, **g Zhang, Tianling Guo, ** Cao, Lixian Wang, Jie Zhang, Xuefei Pang, Feng Gao & Haixia **ao

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Zheng, Y., Zhang, J., Guo, T. et al. Canine interleukin-31 binds directly to OSMRβ with higher binding affinity than to IL-31RA. 3 Biotech 13, 302 (2023). https://doi.org/10.1007/s13205-023-03724-7

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