Startseite Mathematik Immunometabolism of T-cells in COVID-19
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Immunometabolism of T-cells in COVID-19

  • Jian Li , Junping Yin und Christian Kurts
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BIOKYBERNETIKA
Ein Kapitel aus dem Buch BIOKYBERNETIKA

Abstract

Facing post COVID-19 pandemic, it is important to more fully understand the role of T-cells during acute illness and convalescence. CD4+ and CD8+ T-cells were isolated from 184 COVID-19 patients with variant disease severity and 30 healthy individuals. T-cells were subjected to single-cell transcriptomic analysis and to metabolic flux analysis. Results from the two analyses were integrated into a new immunometabolomic scoring system, termed MAS, that was assessed using T-cells from other healthy organs. The MAS scoring system may provide an objective quantitative measure of metabolic activities of T-cells from various body fluids and tissues. In patients with a COVID- 19 infection, peripheral blood CD8+ T-cells from patients with both mild/moderate and severe/critical disease appeared to experience significant metabolic remodeling that favored the use of inositol phosphate, purine, ether lipid and fatty acid pathways. T-cells from patients with a severe/critical COVID-19 disease showed elevated fluxes in metabolic pathways including fatty acid, pentose-phosphate, lysine, cysteinemethionine. During convalescence, metabolism in CD8+ T-cells seemed to maintain a ‘‘pre-active” metabolic state that favored efficient utilization of the metabolic resources. In contrast, circulating CD4+ T-cells appeared to fail to mount a robust metabolic remodeling response during a severe/critical COVID-19 infection, suggesting a low functional reserve that may portend a poor outcome. T-cells from BAL fluid showed suppressed signalling via TCR-AMPK-WNT and lower metabolic utilization of amino-acids, fatty acids, retinol, which might lead to the dysfunction of infected T-cells within the lung. These findings illustrate the functional significance of metabolic remodeling in T-cells in response to a COVID-19 infection. Integration of single-cell transcriptomic data with metabolic flux analysis provides a robust immunological scoring system, which may facilitate future basic science and clinical research in immune response, cellular metabolism, and disease pathogenesis.

Abstract

Facing post COVID-19 pandemic, it is important to more fully understand the role of T-cells during acute illness and convalescence. CD4+ and CD8+ T-cells were isolated from 184 COVID-19 patients with variant disease severity and 30 healthy individuals. T-cells were subjected to single-cell transcriptomic analysis and to metabolic flux analysis. Results from the two analyses were integrated into a new immunometabolomic scoring system, termed MAS, that was assessed using T-cells from other healthy organs. The MAS scoring system may provide an objective quantitative measure of metabolic activities of T-cells from various body fluids and tissues. In patients with a COVID- 19 infection, peripheral blood CD8+ T-cells from patients with both mild/moderate and severe/critical disease appeared to experience significant metabolic remodeling that favored the use of inositol phosphate, purine, ether lipid and fatty acid pathways. T-cells from patients with a severe/critical COVID-19 disease showed elevated fluxes in metabolic pathways including fatty acid, pentose-phosphate, lysine, cysteinemethionine. During convalescence, metabolism in CD8+ T-cells seemed to maintain a ‘‘pre-active” metabolic state that favored efficient utilization of the metabolic resources. In contrast, circulating CD4+ T-cells appeared to fail to mount a robust metabolic remodeling response during a severe/critical COVID-19 infection, suggesting a low functional reserve that may portend a poor outcome. T-cells from BAL fluid showed suppressed signalling via TCR-AMPK-WNT and lower metabolic utilization of amino-acids, fatty acids, retinol, which might lead to the dysfunction of infected T-cells within the lung. These findings illustrate the functional significance of metabolic remodeling in T-cells in response to a COVID-19 infection. Integration of single-cell transcriptomic data with metabolic flux analysis provides a robust immunological scoring system, which may facilitate future basic science and clinical research in immune response, cellular metabolism, and disease pathogenesis.

Kapitel in diesem Buch

  1. Frontmatter I
  2. Prologue I VII
  3. Prologue II XI
  4. Prologue III XIII
  5. Preface XVII
  6. Overview XIX
  7. Contents XXXIII
  8. Part I: Theories
  9. Part I-A: Overarching theory
  10. Introduction 1
  11. Universal axioms in classical Chinese philosophy 5
  12. Category theory for structural characterization 15
  13. Axiomatic bipolar dynamics and their control 45
  14. Part I-B: Systems theories
  15. Introduction 75
  16. Stochastic formalization of agent-oriented systems 79
  17. Simplification of high-dimensional multitempo dynamic models 109
  18. Ideas of symmetry as a biophysical basis of system biomedicine 123
  19. Disorder of multiscale control 149
  20. Part II: Person’s life-sphere
  21. Part II-A: Person’s biosphere
  22. Introduction 185
  23. Mutations as activators of biological evolutionary processes at population levels 189
  24. Immunometabolism of T-cells in COVID-19 209
  25. Part II-A.2: Body’s vital functions
  26. Introduction 245
  27. Structural modeling of vascular networks 249
  28. Mathematical modeling of AI application for the diagnosis of blood flow disorders 283
  29. Modeling of glucose and insulin regulation within the framework of a self-consistent model of the cardiovascular system 303
  30. Hemodynamics in residual myocardial ischemia 319
  31. The quasi-one-dimensional model of the lymph flow in the human lymphatic system 335
  32. An integrate-and-fire mechanism for modeling rhythmicity in the neuroendocrine system 365
  33. Kinetic network modeling of the neuroendocrine hypothalamic-pituitary-adrenal axis dynamics with particular attention on the role of alcohol as a digestif 377
  34. Inflammation and immune response in atherosclerosis 393
  35. Part II-A.3: Body’s motor functions
  36. Introduction 423
  37. A magnetic resonance spectroscopy approach to quantitatively measure GABA and phosphorus level changes in the primary motor cortex elicited by transcranial direct current stimulation 427
  38. Part II-A.4: Body’s operational functions
  39. Introduction 441
  40. The fermionic mind hypothesis–a category-theoretic verification of consciousness 445
  41. Cross-task cognitive workload measurement based on the sample selection of the EEG data 459
  42. Part II-B: Person’s eco-sphere exposures
  43. Introduction 475
  44. The spread of SARS-CoV-2 in Russia and the evolution of the properties of the pathogen 479
  45. Agent-based modeling of epidemic spread via kinetic Monte Carlo method 491
  46. Control of SARS-nCoV outbreaks in China 2020 513
  47. Part II-B.2: Civilization
  48. Introduction 531
  49. Pesticide exposure: Toward holistic environmental modeling 535
  50. Part II-C: Person’s sociosphere exposures
  51. Introduction 559
  52. Evolution of the health system in Shanghai, China, 2016–2020 563
  53. Part III: Technologies
  54. Introduction 577
  55. Design-process automation using functional process blocks 581
  56. Slow/fast dynamic models with applications to engineering problems 601
  57. Part III-B: Information sciences
  58. Introduction 613
  59. Numerical modeling of medical ultrasound using the grid-characteristic method 617
  60. The direct and the inverse magnetic encephalography problem 635
  61. Part III-C: Data-analytic sciences
  62. Introduction 653
  63. Assessing the bioequivalence of two different drugs with the same active ingredient 655
  64. Estimation of adjusted relative risks in log-binomial regression using the Bekhit–Schöpe–Wagenpfeil algorithm 665
  65. Part IV: Clinical medicine
  66. Introduction 679
  67. Finding optimal two-stage combined treatment protocols for a blood cancer model 681
  68. Unraveling the mysteries: Mathematical perspectives on traditional Chinese medicine meridians 697
  69. Epilogue 721
  70. Index 723
https://doi.org/10.1515/9783111341996-012

Kapitel in diesem Buch

  1. Frontmatter I
  2. Prologue I VII
  3. Prologue II XI
  4. Prologue III XIII
  5. Preface XVII
  6. Overview XIX
  7. Contents XXXIII
  8. Part I: Theories
  9. Part I-A: Overarching theory
  10. Introduction 1
  11. Universal axioms in classical Chinese philosophy 5
  12. Category theory for structural characterization 15
  13. Axiomatic bipolar dynamics and their control 45
  14. Part I-B: Systems theories
  15. Introduction 75
  16. Stochastic formalization of agent-oriented systems 79
  17. Simplification of high-dimensional multitempo dynamic models 109
  18. Ideas of symmetry as a biophysical basis of system biomedicine 123
  19. Disorder of multiscale control 149
  20. Part II: Person’s life-sphere
  21. Part II-A: Person’s biosphere
  22. Introduction 185
  23. Mutations as activators of biological evolutionary processes at population levels 189
  24. Immunometabolism of T-cells in COVID-19 209
  25. Part II-A.2: Body’s vital functions
  26. Introduction 245
  27. Structural modeling of vascular networks 249
  28. Mathematical modeling of AI application for the diagnosis of blood flow disorders 283
  29. Modeling of glucose and insulin regulation within the framework of a self-consistent model of the cardiovascular system 303
  30. Hemodynamics in residual myocardial ischemia 319
  31. The quasi-one-dimensional model of the lymph flow in the human lymphatic system 335
  32. An integrate-and-fire mechanism for modeling rhythmicity in the neuroendocrine system 365
  33. Kinetic network modeling of the neuroendocrine hypothalamic-pituitary-adrenal axis dynamics with particular attention on the role of alcohol as a digestif 377
  34. Inflammation and immune response in atherosclerosis 393
  35. Part II-A.3: Body’s motor functions
  36. Introduction 423
  37. A magnetic resonance spectroscopy approach to quantitatively measure GABA and phosphorus level changes in the primary motor cortex elicited by transcranial direct current stimulation 427
  38. Part II-A.4: Body’s operational functions
  39. Introduction 441
  40. The fermionic mind hypothesis–a category-theoretic verification of consciousness 445
  41. Cross-task cognitive workload measurement based on the sample selection of the EEG data 459
  42. Part II-B: Person’s eco-sphere exposures
  43. Introduction 475
  44. The spread of SARS-CoV-2 in Russia and the evolution of the properties of the pathogen 479
  45. Agent-based modeling of epidemic spread via kinetic Monte Carlo method 491
  46. Control of SARS-nCoV outbreaks in China 2020 513
  47. Part II-B.2: Civilization
  48. Introduction 531
  49. Pesticide exposure: Toward holistic environmental modeling 535
  50. Part II-C: Person’s sociosphere exposures
  51. Introduction 559
  52. Evolution of the health system in Shanghai, China, 2016–2020 563
  53. Part III: Technologies
  54. Introduction 577
  55. Design-process automation using functional process blocks 581
  56. Slow/fast dynamic models with applications to engineering problems 601
  57. Part III-B: Information sciences
  58. Introduction 613
  59. Numerical modeling of medical ultrasound using the grid-characteristic method 617
  60. The direct and the inverse magnetic encephalography problem 635
  61. Part III-C: Data-analytic sciences
  62. Introduction 653
  63. Assessing the bioequivalence of two different drugs with the same active ingredient 655
  64. Estimation of adjusted relative risks in log-binomial regression using the Bekhit–Schöpe–Wagenpfeil algorithm 665
  65. Part IV: Clinical medicine
  66. Introduction 679
  67. Finding optimal two-stage combined treatment protocols for a blood cancer model 681
  68. Unraveling the mysteries: Mathematical perspectives on traditional Chinese medicine meridians 697
  69. Epilogue 721
  70. Index 723
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Heruntergeladen am 12.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/9783111341996-012/html
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