能量代谢调控γδT细胞活化的研究进展
Research Progress on Energy Metabolism Regulating the Activation of γδT Cells
DOI: 10.12677/pi.2024.134038, PDF,   
作者: 白金金, 戴 岳*:中国药科大学中药学院中药药理与中医药学系,江苏 南京
关键词: γδT细胞能量代谢细胞活化免疫应答γδT Cells Energy Metabolism Cell Activation Immune Response
摘要: 代谢重编程与T细胞的发育、存活、活化及分化密切相关。T细胞被激活后,对维持细胞生长、增殖以及发挥作用所需的能量增加,需要通过重构细胞代谢来满足。γδT细胞作为T细胞的一种亚群,在自身免疫性疾病和肿瘤中发挥重要作用,已成为近年来的研究热点。本文简要综述脂质代谢、氧化磷酸化、谷氨酰胺代谢和糖酵解在调控γδT细胞活化中的参与和重要性,为构建针对其活化相关疾病的治疗策略提供思路。
Abstract: Metabolic reprogramming is closely associated with the development, survival, activation, and differentiation of T cells. Upon activation, T cells require increased energy to sustain cell growth, proliferation, and effector functions, all of which need the reprogramming of cellular metabolism. γδT cells, as a subset of T cells, have emerged as a research focus in recent years due to their significant roles in autoimmune diseases and cancer. This article briefly reviews the involvement and importance of lipid metabolism, oxidative phosphorylation, glutamine metabolism, and glycolysis in regulating the activation of γδT cells, providing insights for developing therapeutic strategies targeting diseases associated with γδT cell activation.
文章引用:白金金, 戴岳. 能量代谢调控γδT细胞活化的研究进展[J]. 药物资讯, 2024, 13(4): 334-340. https://doi.org/10.12677/pi.2024.134038

参考文献

[1] Rao, A., Agrawal, A., Borthakur, G., Battula, V.L. and Maiti, A. (2024) Gamma Delta T Cells in Acute Myeloid Leukemia: Biology and Emerging Therapeutic Strategies. Journal for ImmunoTherapy of Cancer, 12, e007981. [Google Scholar] [CrossRef] [PubMed]
[2] Guo, J., Chowdhury, R.R., Mallajosyula, V., Xie, J., Dubey, M., Liu, Y., et al. (2024) γδ T Cell Antigen Receptor Polyspecificity Enables T Cell Responses to a Broad Range of Immune Challenges. Proceedings of the National Academy of Sciences, 121, e2315592121. [Google Scholar] [CrossRef] [PubMed]
[3] Gao, Z., Bai, Y., Lin, A., Jiang, A., Zhou, C., Cheng, Q., et al. (2023) Gamma Delta T-Cell-Based Immune Checkpoint Therapy: Attractive Candidate for Antitumor Treatment. Molecular Cancer, 22, Article No. 31. [Google Scholar] [CrossRef] [PubMed]
[4] Ribot, J.C., Lopes, N. and Silva-Santos, B. (2020) γδ T Cells in Tissue Physiology and Surveillance. Nature Reviews Immunology, 21, 221-232. [Google Scholar] [CrossRef] [PubMed]
[5] Bank, I. (2020) The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases. Cells, 9, Article No. 462. [Google Scholar] [CrossRef] [PubMed]
[6] Lim, S.A., Su, W., Chapman, N.M. and Chi, H. (2022) Lipid Metabolism in T Cell Signaling and Function. Nature Chemical Biology, 18, 470-481. [Google Scholar] [CrossRef] [PubMed]
[7] van der Windt, G.J.W., O’Sullivan, D., Everts, B., Huang, S.C., Buck, M.D., Curtis, J.D., et al. (2013) CD8 Memory T Cells Have a Bioenergetic Advantage That Underlies Their Rapid Recall Ability. Proceedings of the National Academy of Sciences, 110, 14336-14341. [Google Scholar] [CrossRef] [PubMed]
[8] Veldhoen, M., Blankenhaus, B., Konjar, Š. and Ferreira, C. (2018) Metabolic Wiring of Murine T Cell and Intraepithelial Lymphocyte Maintenance and Activation. European Journal of Immunology, 48, 1430-1440. [Google Scholar] [CrossRef] [PubMed]
[9] Webb, L.M., Sengupta, S., Edell, C., Piedra-Quintero, Z.L., Amici, S.A., Miranda, J.N., et al. (2020) Protein Arginine Methyltransferase 5 Promotes Cholesterol Biosynthesis-Mediated Th17 Responses and Autoimmunity. Journal of Clinical Investigation, 130, 1683-1698. [Google Scholar] [CrossRef] [PubMed]
[10] Ramos, G.P., Bamidele, A.O., Klatt, E.E., Sagstetter, M.R., Kurdi, A.T., Hamdan, F.H., et al. (2023) G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation. Gastroenterology, 164, 256-271.e10. [Google Scholar] [CrossRef] [PubMed]
[11] Shin, J., O’Brien, T.F., Grayson, J.M. and Zhong, X. (2012) Differential Regulation of Primary and Memory CD8 T Cell Immune Responses by Diacylglycerol Kinases. The Journal of Immunology, 188, 2111-2117. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, F., Beck-García, K., Zorzin, C., Schamel, W.W.A. and Davis, M.M. (2016) Inhibition of T Cell Receptor Signaling by Cholesterol Sulfate, a Naturally Occurring Derivative of Membrane Cholesterol. Nature Immunology, 17, 844-850. [Google Scholar] [CrossRef] [PubMed]
[13] Berod, L., Friedrich, C., Nandan, A., Freitag, J., Hagemann, S., Harmrolfs, K., et al. (2014) De Novo Fatty Acid Synthesis Controls the Fate between Regulatory T and T Helper 17 Cells. Nature Medicine, 20, 1327-1333. [Google Scholar] [CrossRef] [PubMed]
[14] Kidani, Y., Elsaesser, H., Hock, M.B., Vergnes, L., Williams, K.J., Argus, J.P., et al. (2013) Sterol Regulatory Element-Binding Proteins Are Essential for the Metabolic Programming of Effector T Cells and Adaptive Immunity. Nature Immunology, 14, 489-499. [Google Scholar] [CrossRef] [PubMed]
[15] Lopes, N., McIntyre, C., Martin, S., Raverdeau, M., Sumaria, N., Kohlgruber, A.C., et al. (2021) Distinct Metabolic Programs Established in the Thymus Control Effector Functions of γδ T Cell Subsets in Tumor Microenvironments. Nature Immunology, 22, 179-192. [Google Scholar] [CrossRef] [PubMed]
[16] Cheng, H., Wu, R., Gebre, A.K., Hanna, R.N., Smith, D.J., Parks, J.S., et al. (2013) Increased Cholesterol Content in Gammadelta (γδ) T Lymphocytes Differentially Regulates Their Activation. PLOS ONE, 8, e63746. [Google Scholar] [CrossRef] [PubMed]
[17] Nakamizo, S., Honda, T., Adachi, A., Nagatake, T., Kunisawa, J., Kitoh, A., et al. (2017) High Fat Diet Exacerbates Murine Psoriatic Dermatitis by Increasing the Number of Il-17-Producing γδ T Cells. Scientific Reports, 7, Article No. 14076. [Google Scholar] [CrossRef] [PubMed]
[18] Torres‐Hernandez, A., Wang, W., Nikiforov, Y., Tejada, K., Torres, L., Kalabin, A., et al. (2019) γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming. Hepatology, 71, 477-494. [Google Scholar] [CrossRef] [PubMed]
[19] Kobayashi, S., Phung, H.T., Kagawa, Y., Miyazaki, H., Takahashi, Y., Asao, A., et al. (2020) Fatty Acid‐Binding Protein 3 Controls Contact Hypersensitivity through Regulating Skin Dermal Vγ4+ γ/δ T Cell in a Murine Model. Allergy, 76, 1776-1788. [Google Scholar] [CrossRef] [PubMed]
[20] Konjar, Š., Frising, U.C., Ferreira, C., Hinterleitner, R., Mayassi, T., Zhang, Q., et al. (2018) Mitochondria Maintain Controlled Activation State of Epithelial-Resident T Lymphocytes. Science Immunology, 3, eaan2543. [Google Scholar] [CrossRef] [PubMed]
[21] Jaeger, N., Gamini, R., Cella, M., Schettini, J.L., Bugatti, M., Zhao, S., et al. (2021) Single-Cell Analyses of Crohn’s Disease Tissues Reveal Intestinal Intraepithelial T Cells Heterogeneity and Altered Subset Distributions. Nature Communications, 12, Article No. 1921. [Google Scholar] [CrossRef] [PubMed]
[22] Lockhart, A., Mucida, D. and Bilate, A.M. (2024) Intraepithelial Lymphocytes of the Intestine. Annual Review of Immunology, 42, 289-316. [Google Scholar] [CrossRef] [PubMed]
[23] Fahrer, A.M., Konigshofer, Y., Kerr, E.M., Ghandour, G., Mack, D.H., Davis, M.M., et al. (2001) Attributes of γδ Intraepithelial Lymphocytes as Suggested by Their Transcriptional Profile. Proceedings of the National Academy of Sciences, 98, 10261-10266. [Google Scholar] [CrossRef] [PubMed]
[24] Goldberg, E.L., Shchukina, I., Asher, J.L., Sidorov, S., Artyomov, M.N. and Dixit, V.D. (2020) Ketogenesis Activates Metabolically Protective γδ T Cells in Visceral Adipose Tissue. Nature Metabolism, 2, 50-61. [Google Scholar] [CrossRef] [PubMed]
[25] Jiang, Z., He, J., Zhang, B., Wang, L., Long, C., Zhao, B., et al. (2024) A Potential “Anti-Warburg Effect” in Circulating Tumor Cell-Mediated Metastatic Progression? Aging and Disease. [Google Scholar] [CrossRef] [PubMed]
[26] Warburg, O. (1956) On the Origin of Cancer Cells. Science, 123, 309-314. [Google Scholar] [CrossRef] [PubMed]
[27] Ward, P.S. and Thompson, C.B. (2012) Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate. Cancer Cell, 21, 297-308. [Google Scholar] [CrossRef] [PubMed]
[28] Cai, Y., Xue, F., Qin, H., Chen, X., Liu, N., Fleming, C., et al. (2019) Differential Roles of the Mtor-Stat3 Signaling in Dermal γδ T Cell Effector Function in Skin Inflammation. Cell Reports, 27, 3034-3048.e5. [Google Scholar] [CrossRef] [PubMed]
[29] Yamasaki, H., Shimoji, H., Ohshiro, Y. and Sakihama, Y. (2001) Inhibitory Effects of Nitric Oxide on Oxidative Phosphorylation in Plant Mitochondria. Nitric Oxide, 5, 261-270. [Google Scholar] [CrossRef] [PubMed]
[30] Konjar, Š., Ferreira, C., Carvalho, F.S., Figueiredo-Campos, P., Fanczal, J., Ribeiro, S., et al. (2022) Intestinal Tissue-Resident T Cell Activation Depends on Metabolite Availability. Proceedings of the National Academy of Sciences, 119, e2202144119. [Google Scholar] [CrossRef] [PubMed]
[31] Xu, Y., Li, M., Lin, M., Cui, D. and Xie, J. (2024) Glutaminolysis of CD4+ T Cells: A Potential Therapeutic Target in Viral Diseases. Journal of Inflammation Research, 17, 603-616. [Google Scholar] [CrossRef] [PubMed]
[32] Zhu, L., Zhu, X. and Wu, Y. (2022) Effects of Glucose Metabolism, Lipid Metabolism, and Glutamine Metabolism on Tumor Microenvironment and Clinical Implications. Biomolecules, 12, Article No. 580. [Google Scholar] [CrossRef] [PubMed]
[33] Wang, A., Luan, H.H. and Medzhitov, R. (2019) An Evolutionary Perspective on Immunometabolism. Science, 363, eaar3932. [Google Scholar] [CrossRef] [PubMed]
[34] Kim, H. (2011) Glutamine as an Immunonutrient. Yonsei Medical Journal, 52, 892-897. [Google Scholar] [CrossRef] [PubMed]
[35] Cruzat, V.F., Krause, M. and Newsholme, P. (2014) Amino Acid Supplementation and Impact on Immune Function in the Context of Exercise. Journal of the International Society of Sports Nutrition, 11, Article No. 61. [Google Scholar] [CrossRef] [PubMed]
[36] Li, G., Liu, L., Yin, Z., Ye, Z. and Shen, N. (2021) Glutamine Metabolism Is Essential for the Production of IL-17A in γδ T Cells and Skin Inflammation. Tissue and Cell, 71, Article ID: 101569. [Google Scholar] [CrossRef] [PubMed]
[37] He, W., Hu, Y., Chen, D., Li, Y., Ye, D., Zhao, Q., et al. (2022) Hepatocellular Carcinoma‐Infiltrating γδ T Cells Are Functionally Defected and Allogenic Vδ2+ γδ T Cell Can Be a Promising Complement. Clinical and Translational Medicine, 12, e800. [Google Scholar] [CrossRef] [PubMed]
[38] Upadhyay, S., Khan, S. and Hassan, M.I. (2024) Exploring the Diverse Role of Pyruvate Kinase M2 in Cancer: Navigating Beyond Glycolysis and the Warburg Effect. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1879, Article ID: 189089. [Google Scholar] [CrossRef] [PubMed]
[39] Ganapathy-Kanniappan, S. and Geschwind, J.H. (2013) Tumor Glycolysis as a Target for Cancer Therapy: Progress and Prospects. Molecular Cancer, 12, Article No. 152. [Google Scholar] [CrossRef] [PubMed]
[40] Alegre, M., Frauwirth, K.A. and Thompson, C.B. (2001) T-Cell Regulation by CD28 and CTLA-4. Nature Reviews Immunology, 1, 220-228. [Google Scholar] [CrossRef] [PubMed]
[41] Previte, D.M., O’Connor, E.C., Novak, E.A., Martins, C.P., Mollen, K.P. and Piganelli, J.D. (2017) Reactive Oxygen Species Are Required for Driving Efficient and Sustained Aerobic Glycolysis during CD4+ T Cell Activation. PLOS ONE, 12, e0175549. [Google Scholar] [CrossRef] [PubMed]
[42] Chen, X., Cai, Y., Hu, X., Ding, C., He, L., Zhang, X., et al. (2022) Differential Metabolic Requirement Governed by Transcription Factor C-Maf Dictates Innate γδT17 Effector Functionality in Mice and Humans. Science Advances, 8, eabm9120. [Google Scholar] [CrossRef] [PubMed]