• Metabolic reprogramming of CD8⁺ T cells in chronic inflammatory diseases

• Research Associate, Department of Immunology and Inflammation, Imperial College London
• Ph.D., Department of Paediatrics and Adolescent Medicine, The University of Hong Kong
• MPhil, Department of Surgery, The University of Hong Kong
• B.Sc., (Hons), Department of Biochemistry, The University of Hong Kong

Sustained inflammation causes immune cell dysfunction and forms the common pathological basis for many chronic inflammatory diseases including chronic viral infection, cancer and autoimmunity. A key aspect of immune cell dysfunction that underpins the clinical outcome of these chronic conditions is the development of exhausted CD8⁺T cells. Nonetheless, reasons for CD8⁺T cell exhaustion remain incompletely understood. Our laboratory employs the emerging technologies from the field of immunometabolism to assess the effects of sustained inflammation on exhausted T cell differentiation and population diversity. Our long-term goal is to develop metabolism-targeting drugs to regulate T cell immunity in infection, cancer and autoimmunity.

Research articles: 

1. Chen WX, Teo JMN, Yau SW, Wong WMM, Lok CN, Che CM, Javed A, Huang Y, Ma S, Ling GS*. Chronic Type I interferons signaling promotes lipid peroxidation-driven terminal CD8⁺T cell exhaustion and curtails anti-PD-1 treatment efficacy. Cell Reports 2022 Vol 41:111647 doi: https://doi.org/10.1016/j.celrep.2022.111647

2. Lee CH^#, Gray V^#, Teo JMN, Tam AR, Fong CHY, Lui DTW, Chan KH, Hung IFN*, Tan KCB*, Ling GS*. Comparing the B and T Cell-mediated Immune Responses in Patients with Type 2 Diabetes Receiving mRNA or Inactivated COVID-19 Vaccines. Frontiers in Immunology 2022 13:1018393. ^#Joint first author;  *Joint corresponding author

3. Ye ZW, Ong CP, Tang K, Fan Y, Luo C, Zhou R, Luo P, Cheng Y, Gray V, Wang P, Chu H, Chan JFW, To KKW, Chen H, Chen Z, Yuen KY, Ling GS*, Yuan S*, Jin DY*. Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 confers sterilizing immunity in animals. Cellular & Molecular Immunology 2022 Vol 19:588-601. *Joint corresponding author

4. Buang N, Tapeng L, Gray V, Sardini A, Chad W, Lightstone L, Cairns T, Pickering M, Behmoaras J,  Ling GS*, Botto M*. Type I interferons affect the metabolic fitness of CD8⁺T cells from patients with systemic lupus erythematosus. Nature Communications 2021 12:1980 doi: 10.1038/s41467-021-22312-y. *Joint corresponding author 
5. Ling GS, Crawford G, Buang N, Bartok I, Tian K, Thielens NM, Bally I, Harker JA, Ashton-Rickardt PG, Rutschmann S, Strid J, Botto M. C1q restrains autoimmunity and viral infection by regulating CD8⁺ T cell metabolism. Science 2018 Vol 360:558-563.
6. Ling GS*, Bulla R*, Tripodo C*, Rami D*, Agostinis C, Guarnotta C, Zorzet S, Durigutto P, Botto M, Tedesco F. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation. Nature Communications 2016 Feb 1;7:10346. doi: 10.1038/ncomms10346. *Joint first author
7. Ling GS, Bennett J, Woollard KJ, Szajna M, Fossati-Jimack L, Taylor PR, Scott D, Franzoso G, Cook HT, Botto M. Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages. Nature Communications 2014;5:3039. doi: 10.1038/ncomms4039.
8. Ling GS*, Sattler S*, Xu D, Hussaarts L, Romaine A, Zhao H, Fossati-Jimack L, Malik T, Cook HT, Botto M, Lau YL, Smits HH, Liew FY, Huang FP. IL-10-producing regulatory B cells induced by IL-33 (BregIL-33) effectively attenuate mucosal inflammatory responses in the gut. Journal of Autoimmunity 2014 Vol 50:107-22. *Joint first author
9. Bossi F, Tripodo C, Rizzi L, Bulla R, Agostinis C, Guarnotta C, Munaut C, Baldassarre G, Papa G, Zorzet S, Ghebrehiwet B, Ling GS, Botto M, Tedesco F. C1q as a novel player in angiogenesis with therapeutic implication in wound healing. Proceedings of National Academy of Science of the United States of America 2014 Vol 111(11):4209-14.
10. Ling GS*, Fossati-Jimack L*, Cortini A, Szajna M, Malik TH, McDonald JU, Pickering MC, Cook HT, Taylor PR, Botto M. Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells. PLOS One 2013 Vol 8: e57082. *Joint first author
11. Ling GS, Cook HT, Botto M, Lau YL, Huang FP. An essential protective role of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells. Rheumatology 2011 Vol 50: 1773-84.

Review article:

1. Lou Hantao, Ling Guang Sheng, Cao Xuetao. Autoantibodies in systemic lupus erythematosus: From immunopathology to therapeutic target. Journal of Autoimmunity 2022 21:102861

• RGC ECS 2020/2021 (PI)
• RGC GRF 2021/2021 (PI)
• RGC GRF 2022/2023 (PI)
• HMRF 2019 (PI)

• 2015: The Department of Medicine teaching award, Imperial College London

Victor Gray (PhD student 2020-)

Nickolas Jia Ming Teo (HKPF PhD student 2020-)

Wei Xin Chen (PhD student 2021-)

Samantha Wong (Lab technician)