Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55–IL6ST Gene Region in Immature Dendritic Cells
| Autor: | Jorge Mena, Iraide Alloza, Raquel Tulloch Navarro, Ane Aldekoa, Javier Díez García, Ane Villanueva Etxebarria, Cecilia Lindskog, Alfredo Antigüedad, Sabas Boyero, María del Mar Mendibe-Bilbao, Amaya Álvarez de Arcaya, José Luis Sánchez Menoyo, Luciana Midaglia, Noelia Villarrubia, Sunny Malhotra, Xavier Montalban, Luisa María Villar, Manuel Comabella, Koen Vandenbroeck |
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| Přispěvatelé: | Institut Català de la Salut, [Mena J, Alloza I, Tulloch Navarro R, Aldekoa A] Inflammation & Biomarkers Group, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain. [Díez García J] Microscopy Facility, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain. [Villanueva Etxebarria A] Kronikgune Institute for Health Services Research, Barakaldo, Spain. Health Service Research Network on Chronic Diseases Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Bizkaia, Spain. Osakidetza-Basque Health Service, Research Unit, Galdakao University Hospital, Galdakao, Spain. [Midaglia L, Malhotra S, Montalban X, Comabella M] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Tetrahydronaphthalenes
Sgp130 Esclerosi múltiple - Aspectes genètics T-Lymphocytes Immunology sgp130 Autoimmunity multiple sclerosis Benzoates Immunophenotyping ANKRD55 Multiple sclerosis Regulació genètica Cytokine Receptor gp130 Other subheadings::Other subheadings::/genetics [Other subheadings] Humans Immunology and Allergy Genetic Predisposition to Disease Alleles Original Research Medicinsk genetik Otros calificadores::Otros calificadores::/genética [Otros calificadores] Genetic Variation Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases CNS::Multiple Sclerosis [DISEASES] Cell Differentiation autoimmune Dendritic Cells RC581-607 Gene Expression Regulation enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] Leukocytes Mononuclear Immunologic diseases. Allergy Carrier Proteins Medical Genetics IL6ST Biomarkers Autoimmune |
| Zdroj: | Scientia Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Frontiers in Immunology, Vol 12 (2022) Frontiers in Immunology Addi. Archivo Digital para la Docencia y la Investigación instname |
| ISSN: | 1318-6299 |
| Popis: | Autoimmune; Multiple sclerosis Autoinmune; Esclerosis múltiple Autoimmune; Esclerosi múltiple Intronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4+ T lymphocytes of healthy controls. The biological function of ANKRD55, its role in the immune system, and cellular sources of expression other than lymphocytes remain uncharacterized. Here, we show that monocytes gain capacity to express ANKRD55 during differentiation in immature monocyte-derived dendritic cells (moDCs) in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). ANKRD55 expression levels are further enhanced by retinoic acid agonist AM580 but downregulated following maturation with interferon (IFN)-γ and lipopolysaccharide (LPS). ANKRD55 was detected in the nucleus of moDC in nuclear speckles. We also analyzed the adjacent IL6ST, IL31RA, and SLC38A9 genes. Of note, in healthy controls, MS risk SNP genotype influenced ANKRD55 and IL6ST expression in immature moDC in opposite directions to that in CD4+ T cells. This effect was stronger for a partially correlated SNP, rs13186299, that is located, similar to the main MS risk SNPs, in an ANKRD55 intron. Upon analysis in MS patients, the main GWAS MS risk SNP rs7731626 was associated with ANKRD55 expression levels in CD4+ T cells. MoDC-specific ANKRD55 and IL6ST mRNA levels showed significant differences according to the clinical form of the disease, but, in contrast to healthy controls, were not influenced by genotype. We also measured serum sgp130 levels, which were found to be higher in homozygotes of the protective allele of rs7731626. Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo–DC) differentiation as a process potentially influenced by MS risk SNPs. This research was supported by grants to KV from MINECO (SAF2016-74891-R), Instituto de Salud Carlos III (FIS-PI20/00123), Gobierno Vasco RIS3 (Ref. 2019222043), and Red Española de Esclerosis Múltiple (REEM; RD16/0015/0005). NV and LMV were supported by ISCIII (FIS-PI18/00572) and REEM (RD16/0015/0001). RTN is a recipient of a fellowship from the Secretaría Nacional de Ciencia y Tecnología e Innovación (SENACYT; Convocatoria Doctorado de Investigación Ronda III, 2018; Ref. BIDP-III-2018-12) of the Gobierno Nacional, República de Panamá. |
| Databáze: | OpenAIRE |
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