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Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

Author

Listed:
  • Hussein Al-Mossawi

    (University of Oxford)

  • Nicole Yager

    (University of Oxford)

  • Chelsea A. Taylor

    (Weatherall Institute of Molecular Medicine)

  • Evelyn Lau

    (University of Oxford)

  • Sara Danielli

    (Weatherall Institute of Molecular Medicine)

  • Jelle Wit

    (University of Oxford)

  • James Gilchrist

    (University of Oxford)

  • Isar Nassiri

    (Weatherall Institute of Molecular Medicine)

  • Elise A. Mahe

    (Weatherall Institute of Molecular Medicine)

  • Wanseon Lee

    (University of Oxford)

  • Laila Rizvi

    (University of Oxford)

  • Seiko Makino

    (University of Oxford)

  • Jane Cheeseman

    (University of Oxford)

  • Matt Neville

    (University of Oxford)

  • Julian C. Knight

    (University of Oxford)

  • Paul Bowness

    (University of Oxford)

  • Benjamin P. Fairfax

    (Weatherall Institute of Molecular Medicine)

Abstract

IL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases.

Suggested Citation

  • Hussein Al-Mossawi & Nicole Yager & Chelsea A. Taylor & Evelyn Lau & Sara Danielli & Jelle Wit & James Gilchrist & Isar Nassiri & Elise A. Mahe & Wanseon Lee & Laila Rizvi & Seiko Makino & Jane Cheese, 2019. "Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12393-1
    DOI: 10.1038/s41467-019-12393-1
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    Cited by:

    1. Meghan J. Mooradian & Florian J. Fintelmann & Thomas J. LaSalle & Judit Simon & Alexander Graur & Alona Muzikansky & Mari Mino-Kenudson & Sophia Shalhout & Howard L. Kaufman & Russell W. Jenkins & Don, 2024. "Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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