Potential impact of celiac disease genetic risk factors on T cell receptor signaling in gluten-specific CD4+ T cells

Autor: Frits Koning, Yang Li, Joost H.A. Martens, Aarón D. Ramírez-Sánchez, Olivier B. Bakker, Vinod Kumar, Rutger Modderman, Zuzanna Borek, Marie K. Johannesen, Ludvig M. Sollid, Yvonne Kooy-Winkelaar, Filomena Matarese, Knut E.A. Lundin, Iris Jonkers, Niek de Klein, Shuo-Wang Qiao, Cisca Wijmenga, Jeroen van Bergen, Sebo Withoff
Přispěvatelé: Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR)
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Glutens
Science
T cell
Receptors
Antigen
T-Cell
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Proteomic analysis
Inflammation
Biology
Article
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Immune system
Downregulation and upregulation
medicine
Humans
Epigenetics
Molecular Biology
Transcription factor
CD4-positive T cells
Multidisciplinary
Coeliac disease
Gene Expression Profiling
T-cell receptor
nutritional and metabolic diseases
Epigenetics in immune cells
digestive system diseases
Chromatin
Celiac Disease
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
Immunology
Medicine
Cytokines
medicine.symptom
Transcriptome
Biomarkers
Zdroj: Scientific Reports, 11, 1
Scientific Reports, 11(1):9252, 1-15. Nature Publishing Group
Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
Scientific Reports, 11(1). NATURE RESEARCH
Scientific Reports, 11
ISSN: 2045-2322
DOI: 10.1038/s41598-021-86612-5
Popis: Celiac disease is an auto-immune disease in which an immune response to dietary gluten leads to inflammation and subsequent atrophy of small intestinal villi, causing severe bowel discomfort and malabsorption of nutrients. The major instigating factor for the immune response in celiac disease is the activation of gluten-specific CD4+ T cells expressing T cell receptors that recognize gluten peptides presented in the context of HLA-DQ2 and DQ8. Here we provide an in-depth characterization of 28 gluten-specific T cell clones. We assess their transcriptional and epigenetic response to T cell receptor stimulation and link this to genetic factors associated with celiac disease. Gluten-specific T cells have a distinct transcriptional profile that mostly resembles that of Th1 cells but also express cytokines characteristic of other types of T-helper cells. This transcriptional response appears not to be regulated by changes in chromatin state, but rather by early upregulation of transcription factors and non-coding RNAs that likely orchestrate the subsequent activation of genes that play a role in immune pathways. Finally, integration of chromatin and transcription factor binding profiles suggest that genes activated by T cell receptor stimulation of gluten‑specific T cells may be impacted by genetic variation at several genetic loci associated with celiac disease.
Databáze: OpenAIRE
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