{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim T"],"funding":["Bristol-Myers Squibb Company | Bristol-Myers Squibb Canada","NCATS NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke","U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Center for Research Resources","U.S. Department of Health &amp; Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","NHGRI NIH HHS","NINDS NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Human Genome Research Institute","NIAMS NIH HHS","Arthritis National Research Foundation"],"pagination":["2150"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923805"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Fine-mapping and functional studies implicate rs117701653, a non-coding single nucleotide polymorphism in the CD28/CTLA4/ICOS locus, as a risk variant for rheumatoid arthritis and type 1 diabetes. Here, using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated risk allele is functional, reducing affinity for the inhibitory chromosomal regulator SMCHD1 to enhance expression of inducible T-cell costimulator (ICOS) in memory CD4<sup>+</sup> T cells from healthy donors. Higher ICOS expression is paralleled by an increase in circulating T peripheral helper (Tph) cells and, in rheumatoid arthritis patients, of blood and joint fluid Tph cells as well as circulating plasmablasts. Correspondingly, ICOS ligation and carriage of the rs117701653 "],"journal":["Nature communications"],"pubmed_title":["Non-coding autoimmune risk variant defines role for ICOS in T peripheral helper cell development."],"pmcid":["PMC10923805"],"funding_grant_id":["R01AR065538","P30 AR070549","AR078769","P30AR069625","R01 AR073201","R01AI024717","R01 AR077607","R01 HG010730","R01 AR075906","R01AR063759","R01 NS099068","K08AR072791","P30AR070253","R01 AR073228","R01AR073228","R01 AR065538","P30 AR069625","IM101-835","UL1TR002541","R01AR077607","R01 AR063759","R01AR075906","U01AI130830","UL1 TR002541","P30AR072577","U01 AI130830","T32 AR007530","T32 AR007611","P30 AR072577","R01HG010730","R01AR073201","R01 AI024717","P30 AR070253","K08 AR072791","R01NS099068","R01 AR078769"],"pubmed_authors":["Hackert N","Chiu DJ","Baglaenko Y","Weirauch MT","Rao DA","Raychaudhuri S","Nigrovic PA","Laza-Briviesca R","Westra HJ","Darbousset R","Sparks JA","Aguiar VRC","Kim T","Koh B","Wang Q","Martinez-Bonet M","Chen X","Gutierrez-Arcelus M"],"additional_accession":[]},"is_claimable":false,"name":"Non-coding autoimmune risk variant defines role for ICOS in T peripheral helper cell development.","description":"Fine-mapping and functional studies implicate rs117701653, a non-coding single nucleotide polymorphism in the CD28/CTLA4/ICOS locus, as a risk variant for rheumatoid arthritis and type 1 diabetes. Here, using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated risk allele is functional, reducing affinity for the inhibitory chromosomal regulator SMCHD1 to enhance expression of inducible T-cell costimulator (ICOS) in memory CD4<sup>+</sup> T cells from healthy donors. Higher ICOS expression is paralleled by an increase in circulating T peripheral helper (Tph) cells and, in rheumatoid arthritis patients, of blood and joint fluid Tph cells as well as circulating plasmablasts. Correspondingly, ICOS ligation and carriage of the rs117701653 ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-15T14:02:14.312Z","creation":"2024-11-09T19:15:22.647Z"},"accession":"S-EPMC10923805","cross_references":{"pubmed":["38459032"],"doi":["10.1038/s41467-024-46457-8"]}}