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

被引：32

作者：

Al-Mossawi, Hussein ^{[1
]}

Yager, Nicole ^{[1
]}

Taylor, Chelsea A. ^{[2
]}

Lau, Evelyn ^{[3
]}

Danielli, Sara ^{[2
]}

de Wit, Jelle ^{[1
]}

Gilchrist, James ^{[3
]}

Nassiri, Isar ^{[2
]}

Mahe, Elise A. ^{[2
]}

Lee, Wanseon ^{[3
]}

Rizvi, Laila ^{[1
]}

Makino, Seiko ^{[3
]}

Cheeseman, Jane ^{[4
]}

Neville, Matt ^{[4
]}

Knight, Julian C. ^{[3
]}

Bowness, Paul ^{[1
]}

Fairfax, Benjamin P. ^{[2
]}

机构：

[1] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[2] Weatherall Inst Mol Med, Dept Oncol, Oxford, England

[3] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[4] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; RECEPTOR; IL-7; CELLS; POLARIZATION; CYTOKINES; VARIANTS; CLONING;

D O I：

10.1038/s41467-019-12393-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 spondy-loarthritis 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.

引用

页数：11

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