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Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele.
Al-Mossawi, Hussein; Yager, Nicole; Taylor, Chelsea A; Lau, Evelyn; Danielli, Sara; de Wit, Jelle; Gilchrist, James; Nassiri, Isar; Mahe, Elise A; Lee, Wanseon; Rizvi, Laila; Makino, Seiko; Cheeseman, Jane; Neville, Matt; Knight, Julian C; Bowness, Paul; Fairfax, Benjamin P.
  • Al-Mossawi H; Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
  • Yager N; Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
  • Taylor CA; Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Lau E; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Danielli S; Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • de Wit J; Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
  • Gilchrist J; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Nassiri I; Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Mahe EA; Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Lee W; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Rizvi L; Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
  • Makino S; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Cheeseman J; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
  • Neville M; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
  • Knight JC; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Bowness P; Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
  • Fairfax BP; Department of Oncology, Weatherall Institute of Molecular Medicine, Oxford, UK. benjamin.fairfax@oncology.ox.ac.uk.
Nat Commun ; 10(1): 4575, 2019 10 08.
Article en En | MEDLINE | ID: mdl-31594933
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espondilitis Anquilosante / Monocitos / Autoinmunidad / Interleucina-7 / Subunidad alfa del Receptor de Interleucina-7 Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2019 Tipo del documento: Article
Texto completo
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XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Espondilitis Anquilosante / Monocitos / Autoinmunidad / Interleucina-7 / Subunidad alfa del Receptor de Interleucina-7 Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2019 Tipo del documento: Article