Epigenetic regulation of lymphocyte differentiation and function. T cells can be programmed into different functional subsets that can promote or suppress inflammation and disease. Differentiation and functional plasticity of T cells is dependent on the epigenetic regulator Ezh2 (Tumes et al, Immunity, 2013). We are using modern technologies such as chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) to provide a global view of gene regulation in T cells. This information is being used to determine how T cell differentiation and plasticity is regulated and to define new ways to control T cell function in diseases such as allergy and cancer.
Allergic disease of the airways. Airway mucosal tissue is a specialised barrier capable of protecting against infection while allowing airflow to the lungs and absorption of oxygen into the body. Inflammation of the airways results in accumulation of immune cells in lymphoid structures close to the mucosal surface. We are using cutting edge techniques such as single cell RNA-Sequencing and a human airway tissue xenograft model to dissect the inflammatory pathways operating in patients with upper airways disease.
Allergic disease of the skin. The skin is the largest barrier tissue in our body and provides both physical and immunological protection from infection. Mast cells are activated via antigen-mediated cross-linking of IgE bound to their surface, a process that is centrally involved in inflammatory skin diseases such as atopic dermatitis. We are defining novel signalling pathways that regulate IgE-driven mast cell activity and testing new topically applied drugs to inhibit allergic skin diseases.
Yip KH, Papadopoulos M, Pant H, Tumes DJ*. The role of invariant T cells in inflammation of the skin and airways. Sem. Immunopathol. Impact Factor (IF):6.4. In Press (2019). *corresponding author.
Tumes DJ*, Hirahara K, Papadopoulos M, Shinoda K, Onodera A, Kumagai J, Yip KH, Pant H, Kokubo K, Kiuichi K, Aoki A, Obata-Ninomiya K, Tokoyoda K, Endo Y, Kimura MY, Nakayama T. Ezh2 controls development of natural killer T cells that cause spontaneous asthma-like pathology in mice. J. Allergy Clin. Immunol. IF:13.2. In Press (2019). *corresponding author.
Lynn MA*, Tumes DJ*, Choo JM, Sribnaia A, Blake SJ, Leong LEX, Young GP, Marshall HS, Wesselingh SL, Rogers GB, Lynn DJ. Early-life antibiotic-driven dysbiosis in mice leads to impaired antibody responses and enhanced T cell cytokine recall responses to vaccination. Cell Host Microbe. IF:17.8. 23(5):653-660.e5. (2018). *equal contribution.
Tumes DJ*, Papadopoulos M, Endo Y, Onodera A, Hirahara K, and Nakayama T. Epigenetic regulation of T-helper cell differentiation, memory, and plasticity in allergic asthma. Immunol. Rev. IF:9.5. Vol. 278(1):8-19 (2017). *corresponding author.
Yip KH, Kolesnikoff N, Hauschild N, Biggs L, Lopez AF, Galli SJ, Kumar S, Grimbaldeston MA. The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation. Nat. Commun. IF:12.3. 27;7:13198 (2016).
Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, Tumes DJ, Okamoto Y. Th2 Cells in Health and Disease. Annu. Rev. Immunol. IF:35.5. 35:53-84 (2017).
Yip KH*, Kolesnikoff N*, Yu C, Hauschild N, Taing H, Biggs L, Goltzman D, Gregory PA, Anderson PH, Samuel MS, Galli SJ, Lopez AF, Grimbaldeston MA. Mechanisms of vitamin D₃ metabolite repression of IgE-dependent mast cell activation. J. Allergy Clin. Immunol. IF:13.2. 133(5):1356-64, (2014). *equal contribution.
Pant H, Hughes A, Schembri M, Miljkovic D, Krumbiegel D. CD4+ and CD8+ regulatory T cells in chronic rhinosinusitis mucosa. Am. J. Rhinol. Allergy. IF:1.9. 28(2):83-89 (2014).
Pant H, Hughes A, Miljkovic D, Schembri M, Wormald P, Macardle P, Grose R, Zola H, Krumbiegel D. Accumulation of effector memory CD8+ T cells in nasal polyps. Am. J. Rhinol. Allergy. IF:1.9. 27(5):e117-26 (2013).
Tumes DJ, OnoderaA, SuzukiA, ShinodaK, EndoY, IwamuraC, HosokawaH, KosekiH, TokoyodaK, SuzukiY, Motohashi S, and Nakayama T. The polycomb protein Ezh2 regulates differentiation and plasticity of CD4 T helper type-1 and type-2 cells. Immunity. IF:22.8. 39(5):819-32 (2013).