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Versus Arthritis Career Development Fellow
Research area
Regulatory T cell (Treg) function in health versus autoimmunity.
Research programme
Research summary
CD4+ Regulatory T cells (Tregs) are crucial to maintain tolerance, balancing effector T cell responses to harmful agents and suppressing unwanted responses. However, too little control may lead to autoimmunity (e.g. juvenile idiopathic arthritis or type 1 diabetes), while too much control may contribute to the development of cancers. Co-stimulatory and co-inhibitory receptors are crucial to determine functional outcomes upon activation. We found an imbalance of co-receptor expression at the site of inflammation and mutations in co-receptor genes have been associated with autoimmunity.
We focus on the co-receptor family CD226, TIGIT and CD96; receptors highly expressed on Tregs but with little understanding of their function. We use cellular and molecular immunology techniques, including the cutting-edge gene-editing system CRISPR-Cas9, to elucidate the CD226, TIGIT and CD96 signalling, receptor-receptor and receptor-ligand interactions and study their role in primary human Treg function in health and disease.
Publications
- Selected publications
- Lam AJ, Lin DTS, Gillies JK, Uday P, Pesenacker AM, Kobor MS, Levings MK. Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity. Cell Rep. 2021 Aug 3;36(5):109494. doi: 10.1016/j.celrep.2021.109494. PMID: 34348163.
- Pesenacker AM, Chen V, Gillies J, Speake C, Marwaha AK, Sun A, Chow S, Tan R, Elliott T, Dutz JP, Tebbutt SJ, Levings MK. Treg gene signatures predict and measure type 1 diabetes trajectory. JCI Insight. 2019 Mar 21;4(6). pii: 123879. doi: 10.1172/jci.insight.123879. eCollection 2019 Mar 21. PubMed PMID: 30730852; PubMed Central PMCID: PMC6483004
- Halliday N, Williams C, Kennedy A, Waters E, Pesenacker AM, Soskic B, Hinze C, Hou TZ, Rowshanravan B, Janman D, Walker LSK, Sansom DM. CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4. Front Immunol. 2020 Dec 8;11:600000. doi: 10.3389/fimmu.2020.600000. PMID: 33363541; PMCID: PMC7753196.
- Speake C, Skinner SO, Berel D, Whalen E, Dufort MJ, Young WC, Odegard JM, Pesenacker AM, Gorus FK, James EA, Levings MK, Linsley PS, Akirav EM, Pugliese A, Hessner MJ, Nepom GT, Gottardo R, Long SA. A composite immune signature parallels disease progression across T1D subjects. JCI Insight. 2019 Dec 5;4(23):e126917. doi: 10.1172/jci.insight.126917. PMID: 31671072; PMCID: PMC6962023.
- Hoeppli RE, Pesenacker AM. Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis-Insights From Other Diseases. Front Immunol. 2019 Jan 25;10:46. doi: 10.3389/fimmu.2019.00046. PMID: 30740105; PMCID: PMC6355674.
- Pesenacker AM, Wang AY, Singh A, Gillies J, Kim Y, Piccirillo CA, Nguyen D, Haining WN, Tebbutt SJ, Panagiotopoulos C, Levings MK. A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes. Diabetes. 2016 Apr;65(4):1031-9. doi: 10.2337/db15-0572. Epub 2016 Jan 19. PubMed PMID: 26786322
- Patterson SJ, Pesenacker AM, Wang AY, Gillies J, Mojibian M, Morishita K, Tan R, Kieffer TJ, Verchere CB, Panagiotopoulos C, Levings MK. T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression. J Clin Invest. 2016 Mar 1;126(3):1039-51. doi: 10.1172/JCI83987. Epub 2016 Feb 8. PubMed PMID: 26854929; PubMed Central PMCID: PMC4767359
- Pesenacker AM, Bending D, Ursu S, Wu Q, Nistala K, Wedderburn LR. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood. 2013 Apr 4;121(14):2647-58. doi: 10.1182/blood-2012-08-443473. Epub 2013 Jan 25. PubMed PMID: 23355538; PubMed Central PMCID: PMC3617631.
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