the il23r r381q gene variant protects against immune-mediated diseases by impairing il-23-induced th17 effector response in humans的il23r r381q基因变体预防免疫介导的疾病的损害il-23-induced th17效应反应人类.pdfVIP

The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans 1 1,3 1 1 1 Paola Di Meglio , Antonella Di Cesare , Ute Laggner , Chung-Ching Chu , Luca Napolitano , Federica 1 1 2 2 3 1 Villanova , Isabella Tosi , Francesca Capon , Richard C. Trembath , Ketty Peris , Frank O. Nestle * 1 St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, United Kingdom, 2 Department of Medical and Molecular Genetics, King’s College London and NIHR Biomedical Research Centre, London, United Kingdom, 3 Department of Dermatology, University of L’Aquila, L’Aquila, Italy Abstract IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn’s disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A) and common (G) allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced I