Human Single Cell Immunology
Recent advances in single cell technologies such as mass cytometry and single cell RNA-Seq have revealed high levels of heterogeneity among immune cells. Accordingly, Foxp3 expressing CD4+ regulatory T-cells (Tregs) need to adapt to diverse immunological environments Tregs themselves must show a diversity of functional states. Recent evidence demonstrates that Tregs partially mirror the phenotype of effector T-cell subset such as Th1, Th17 and Tfh cells.
In particular, T-follicular regulatory cells (Tfr) expressing the Tfh lineage defining transcription factor BCL6 are able to gain expression of the chemokine receptor CXCR5 and travel to the B-cell follicle where they act to suppress antibody production. Previously we have demonstrated that Tregs and Tfr control the formation of T-follicular helper cells and the resulting B-cell germinal center reaction via the co-inhibitory receptor CTLA-4 (Wing et al, Immunity 2014). Recently we found that there is a fundamental split in effector Treg subtypes with BCL6 expressing Tfr forming an IL-2 inhibited branch requiring them to downregulate the canonical Treg marker CD25 (IL2RA) in order to reach the germinal center (Wing et al, PNAS 2017). We have also found CXCR5 expressing Tfr like cells present in human blood.
Given the complexity of the underlying biology a high dimensional approach, using mass cytometry (CyTOF), has many benefits for both the understanding of Treg heterogeneity and characterising the wide ranging effects of their impairment. Currently we are applying mass cytometry and other single cell techniques to a number of issues such as to explore the diversity of Tregs and consequences of Treg impairment in a variety of settings such as autoimmunity and cancer (Wing et al, Immunity 2019).
James Badger Wing 准教授
Mass Cytometry, Immune regulation, T-cell-B-cell interactions.
|2003||PhD University of Sheffield: Sheffield, UK (-2007)|
|1999||Degree in medical microbiology, University of Surrey, Guildford, UK (-2003)|
|2019 -||Associate Professor (Human Immunology) IFReC, Osaka University|
|2017||Associate Professor (Experimental Immunology) IFReC, Osaka University|
|2012||Assistant Professor (Experimental Immunology) IFReC, Osaka University|
|2010||JSPS fellow (Experimental Immunology) IFReC, Osaka University|
|2008||Post-doctoral research fellow. University of Sheffield: Sheffield, UK|
- James Badger Wing 准教授
- Jonas N. Søndergaard 助教
- Janyerkye Tulyeu 研究員
- 石井 利佳 技術職員
- Wing, JB., Tanaka, A., & Sakaguchi, S. Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer. Immunity, 2019, 50(2), 302–316. Review DOI/10.1016/J.IMMUNI.2019.01.020
- Cossarizza A,…150 authors…,Wing, JB….16 authors… Zychlinsky A. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur J Immunol. 2019 Oct;49(10):1457-1973. doi: 10.1002/eji.201970107.
- Wing, JB., Tekgüç, M., & Sakaguchi, S. Control of Germinal Center Responses by T-Follicular Regulatory Cells. Frontiers in Immunology, 2018, 9, 1910. Review. DOI/10.3389/fimmu.2018.01910
- Ha, D., Tanaka, A., Kibayashi, T., Tanemura, A., Sugiyama, D., Wing, JB., … 6 authors… Sakaguchi, S. (2019). Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody. Proc Natl Acad Sci U S A. 2019. 116(2), 609–618. DOI/10.1073/pnas.1812186116
- Wing JB, Kitagawa Y, Locci M, Hume H, Tay C, Morita T, Kidani Y, Matsuda K, Inoue T, Kurosaki T, Crotty S, Coban C, Ohkura N, Sakaguchi S. A distinct subpopulation of CD25- T-follicular regulatory cells localizes in the germinal centers. Proc Natl Acad Sci U S A. 2017 Jul 11. pii: 201705551. DOI: 10.1073/pnas.1705551114.
- Glatman Zaretsky, A., C. Konradt, F. Depis, Wing JB, R. Goenka, DG. Atria, JS. Silver, S. Cho, AI. Wolf, WJ. Quinn, JB. Engiles, DC. Brown, D. Beiting, J. Erikson, D. Allman, MP. Cancro, S. Sakaguchi, LF. Lu, CO. Benoist, and CA. Hunter. T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow. Cell Rep, 2017. 18(8): p. 1906-1916. DOI: 10.1016/j.celrep.2017.01.067.
- Morita, T., Y. Shima, Wing JB, S. Sakaguchi, A. Ogata, and A. Kumanogoh. The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis. PloS one, 2016. 11(9). DOI: 10.1371/journal.pone.0162306.
- Ohnmacht, C., J.H. Park, S. Cording, Wing JB, K. Atarashi, Y. Obata, V. Gaboriau-Routhiau, R. Marques, S. Dulauroy, M. Fedoseeva, M. Busslinger, N. Cerf-Bensussan, I.G. Boneca, D. Voehringer, K. Hase, K. Honda, S. Sakaguchi, and G. Eberl. MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science, 2015. 349(6251): p. 989-93 DOI: 10.1126/science.aac4263.
- Schubert, D., C. Bode, R. Kenefeck, T.Z. Hou, Wing JB, …34 authors…, B. Grimbacher. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nature medicine, 2014. 20(12): p. 1410-6. DOI: 10.1038/nm.3746.
- Maeda, Y., H. Nishikawa, D. Sugiyama, D. Ha, M. Hamaguchi, T. Saito, M. Nishioka, Wing JB, D. Adeegbe, I. Katayama, and S. Sakaguchi. Detection of self-reactive CD8(+) T cells with an anergic phenotype in healthy individuals. Science, 2014. 346(6216): p. 1536-40. DOI: 10.1126/science.aaa1292.
- Wing JB, W. Ise, T. Kurosaki, and S. Sakaguchi. Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. Immunity, 2014. 41(6): p. 1013-25. DOI: 10.1016/j.immuni.2014.12.006.
- Wing JB, Smart L, Borrow R, Findlow J, Findlow H, Heath AW, Read RC. Kinetics of immune responses to nasal challenge with meningococcal polysaccharide one year after serogroup-C glycoconjugate vaccination. Clin Infect Dis. 2011 Jun;52(11): p. 1317-23. DOI: 10.1093/cid/cir198
- Wing JB*, Darton TC*, Lees A, Heath AW, Read RC. Adult survivors of invasive pneumococcal disease exhibit defective B cell function. Clin Infect Dis. 2011 May;52(9): p. 1133-6. DOI: 10.1093/cid/cir126. *Joint first authors.