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The contribution from interleukin-27 towards rheumatoid inflammation: insights from gene expression

Abstract

We aimed to assess expression of genes encoding the heterodimeric IL-27 cytokine and constituent subunits of the Il-27 receptor in rheumatoid arthritis (RA), including in extra-articular, subcutaneous rheumatoid nodules. Comparing between nodules and joint synovia, significantly elevated expression of IL27A within nodules, and comparable IL27B expression, identified nodules as a significant source of IL-27 in RA. T-lymphocytes were the main source of IL27RA transcript, and IL27RA expression correlated with a number of plasma cytokines, as well as tissue TNF expression in both nodules and RA synovia. In synovia, correlations between IL27A, IL27RA IL17A and CD21L expression, and significantly elevated expression of the genes encoding IL-27, associated the presence of IL-27 with B cell-dominated synovial inflammation. Impact from nodule derived IL-27 on systemic or synovial inflammation in RA remains unknown and further study of these implications is required. Our study raises questions regarding the appropriate circumstances for the blockade or administration of IL-27 as a potential therapeutic adjunct in RA.

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Fig. 1: Gene expression in synovial and nodule tissues.
Fig. 2: Significant correlations in gene expression within rheumatoid tissues.
Fig. 3: Gene expression in paired synovia and nodules.
Fig. 4: Expression of IL27A and IL27RA in rheumatoid subcutaneous nodule tissue.
Fig. 5: IL-27 localisation in subcutaneous nodules.
Fig. 6: Expression of IL-27 and IL27R in synovial tissue.

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Acknowledgements

Thanks to Sam Smith-Bell for his help with IL6 and TNF expression data and Jill Drake for help with coordination of patient data. Histology support was provided by the Otago micro and nanoscale imaging unit. This work was supported by grants from the Health Research Council of New Zealand and an Otago Medical Research Foundation, Jack Thomson grant.

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Correspondence to Paul A. Hessian.

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Millier, M.J., Lazaro, K., Stamp, L.K. et al. The contribution from interleukin-27 towards rheumatoid inflammation: insights from gene expression. Genes Immun 21, 249–259 (2020). https://doi.org/10.1038/s41435-020-0102-z

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