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

• DOI: 10.1038/s41467-019-12393-1
• Publication Date: 2019-10-08T10:24:04Z
• Authors: Hussein Al-Mossawi; Nicole Yager; Chelsea A. Taylor; Evelyn Lau; Sara Danielli; Jelle de Wit; James Gilchrist; Isar Nassiri; Elise A. Mahe; Wanseon Lee; Laila Rizvi; Seiko Makino; Jane Cheeseman; Matt Neville; Julian C. Knight; Paul Bowness; Benjamin P. Fairfax
• Keywords: Lipopolysaccharides; Science; Autoimmunity; Polymorphism, Single Nucleotide; Article; Monocytes; DEAD-box RNA Helicases; Interleukin-7 Receptor alpha Subunit; 03 medical and health sciences; Synovial Fluid; Humans; Genetic Predisposition to Disease; Spondylitis, Ankylosing; Monocytes and macrophages; Alleles; 0303 health sciences; Disease genetics; Sequence Analysis, RNA; Interleukins; Gene Expression Profiling; Interleukin-7; Q; Healthy Volunteers; Up-Regulation; Single-Cell Analysis; Ankylosing spondylitis

AbstractIL-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.