Electronic Resource
A Crohn's disease-associated IL2RA enhancer variant determines the balance of T cell immunity by regulating responsiveness to IL-2 signaling.
| العنوان: | A Crohn's disease-associated IL2RA enhancer variant determines the balance of T cell immunity by regulating responsiveness to IL-2 signaling. |
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| المؤلفون: | Goldberg R., Clough J.N., Roberts L.B., Sanchez J., Kordasti S., Petrov N., Hertweck A., Lorenc A., Jackson I., Tasker S., Appios A., Omer O., Parkes M., Prescott N., Jenner R.G., Irving P.M., Lord G.M. |
| بيانات النشر: | NLM (Medline) United Kingdom 2021-06-23 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | BACKGROUND AND AIMS: Differential responsiveness to interleukin (IL)-2 between effector CD4+ T cells (Teff) and regulatory T cells (Treg) is a fundamental mechanism of immunoregulation. The single nucleotide polymorphism rs61839660, located within IL2RA (CD25), has been associated with the development of Crohn's disease. We sought to identify the T cell immune phenotype of IBD patients who carry this SNP. METHOD(S): Teff and Treg were isolated from individuals homozygous (TT), heterozygous (CT) or wild type (CC) for the minor allele at rs61839660, and used for phenotyping (flow cytometry, Cytometry Time Of Flight) functional assays or T cell receptor (TCR) sequencing. Phosphorylation of signal transducer and activator of transcription 5 (STAT5) was assessed in response to IL-2, IL-7 and in the presence of basiliximab, a monoclonal antibody directed against CD25. Teff proinflammatory cytokine expression levels were assessed by reverse transcription quantitative polymerase chain reaction after IL-2 and/or TCR stimulation. RESULT(S): Presence of the minor T allele enhances CD25 expression leading to increased STAT5 phosphorylation and proinflammatory cytokine transcript expression by Teff in response to IL-2 stimulation in vitro. Teff from TT individuals demonstrate a more activated gut homing phenotype. TCR sequencing analysis suggests that TT patients may have a reduced clonal capacity to mount an optimal regulatory T cell response. CONCLUSION(S): rs61839660 regulates the responsiveness of T cells to IL-2 signaling by modulating CD25 expression. As low dose IL-2 is being trialed as a selective Treg modulator in CD, these findings highlight the potential for adverse effects in patients with this genotype.Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. |
| مصطلحات الفهرس: | Article |
| URL: | Journal of Crohn's & Colitis LibKey Link |
| الاتاحة: | Open access content. Open access content |
| Other Numbers: | AUSHL oai:repository.monashhealth.org:1/43234 Journal of Crohn's & colitis. (no pagination), 2021. Date of Publication: 12 Jun 2021. https://repository.monashhealth.org/monashhealthjspui/handle/1/43234 34120187 [http://www.ncbi.nlm.nih.gov/pubmed/?term=34120187] (Goldberg, Clough, Roberts, Sanchez, Lorenc, Jackson, Tasker, Appios, Omer, Irving, Lord) School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London SE1 9RT, United Kingdom (Goldberg) School of Clinical Sciences, Monash University, Australia (Goldberg) Department of Gastroenterology, Monash Health, Australia (Clough, Omer, Irving) IBD Unit, Gastroenterology Department, Guy's and St Thomas' NHS Trust (Clough, Roberts, Petrov, Jackson, Prescott, Lord) National Institute for Health Research Biomedical Research Centre, Guy's and St Thomas' NHS Trust and King's College London, United Kingdom (Kordasti) CRUK-KHP Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London (Hertweck, Jenner) UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom (Parkes) Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, United Kingdom (Prescott) Medical and Molecular Genetics, Kings College London, United Kingdom (Lord) Faculty of Biology, Medicine and Health, University of Manchester, United Kingdom 1305131693 |
| المصدر المساهم: | MONASH HEALTH LIBRS From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1305131693 |
| قاعدة البيانات: | OAIster |
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