Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T- and B-cell interactions

Matteo Barberis , Alejandra Rojas López

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (3) : e1626

PDF
Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (3) : e1626 DOI: 10.1002/ctm2.1626
PERSPECTIVE

Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T- and B-cell interactions

Author information +
History +
PDF

Abstract

The interplay between the immune system and the metabolic state of a cell is intricate. In all phases of an immune response, the corresponding metabolic changes shall occur to support its modulation, in addition to the signalling through the cytokine environment and immune receptor stimulation. While autoimmune disorders may develop because of a metabolic imbalance that modulates switching between T-cell phenotypes, the effects that the interaction between T and B cells have on one another's cellular metabolism are yet to be understood in disease context. Here, we propose a perspective which highlights the potential of targeting metabolism to modulate T- and B-cell subtypes populations as well as T–B and B–T cell interactions to successfully treat autoimmune disorders. Specifically, we envision how metabolic changes can tip the balance of immune cells interactions, through definite mechanisms in both health and disease, to explain phenotype switches of B and T cells. Within this scenario, we highlight targeting metabolism that link inflammation, immunometabolism, epigenetics and ageing, is critical to understand inflammatory disorders. The combination of treatments targeting immune cells that cause (T/B) cell phenotype imbalances, and the metabolic pathways involved, may increase the effectiveness of treatment of autoimmune disorders, and/or ameliorate their symptoms to improve patients’ quality of life.

Keywords

ageing / autoimmune disorders / B-cell phenotypes / metabolic disorders / metabolic switches / systems immunology / T-cell phenotypes

Cite this article

Download citation ▾
Matteo Barberis, Alejandra Rojas López. Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T- and B-cell interactions. Clinical and Translational Medicine, 2024, 14(3): e1626 DOI:10.1002/ctm2.1626

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Barberis M, Rojas López A. T cell phenotype switching in autoimmune disorders: clinical significance of targeting metabolism. Clin Transl Med. 2022;12(7):e898.

[2]

Makowski L, Chaib M, Rathmell JC. Immunometabolism: from basic mechanisms to translation. Immunol Rev. 2020; 295(1):5-14.

[3]

Chi H. Immunometabolism at the intersection of metabolic signalling, cell fate, and systems immunology. Cell Mol Immunol. 2022;19(3):299-302.

[4]

Akkaya M, Pierce SK. From zero to sixty and back to zero again: the metabolic life of B cells. Curr Opin Immunol. 2019;57:1-7.

[5]

Chi H. Regulation and function of mTOR signalling in T cell fate decisions. Nat Rev Immunol. 2012;12(5):325-338.

[6]

Winer DA, Winer S, Shen L, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17(5):610-617.

[7]

Buang N, Tapeng L, Gray V, et al. Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus. Nat Commun. 2021;12(1):1980.

[8]

Kono M, Yoshida N, Tsokos GC. Metabolic control of T cells in autoimmunity. Curr Opin Rheumatol. 2020;32(2):192-199.

[9]

Michalek RD, Rathmell JC. The metabolic life and times of a T-cell. Immunol Rev. 2010;236:190-202.

[10]

Marchingo JM, Cantrell DA. Protein synthesis, degradation, and energy metabolism in T cell immunity. Cell Mol Immunol. 2022;19(3):303-315.

[11]

Kramer PA, Prichard L, Chacko B, et al. Inhibition of the lymphocyte metabolic switch by the oxidative burst of human neutrophils. Clin Sci. 2015;129(6):489-504.

[12]

Dong L, He Y, Cao Y, et al. Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity. Immunology. 2021;163(1):19-32.

[13]

Linterman MA, Rigby RJ, Wong RK, et al. Follicular helper T cells are required for systemic autoimmunity. J Exp Med. 2009;206(3):561-576.

[14]

Wei X, Niu X. T follicular helper cells in autoimmune diseases. J Autoimmun. 2023;134:102976.

[15]

Yao Y, Ma J-F, Chang C, et al. Immunobiology of T cells in Sjögren's syndrome. Clin Rev Allergy Immunol. 2021;60(1):111-131.

[16]

Yang J, Yang X, Zou H, et al. Oxidative stress and Treg and Th17 dysfunction in systemic lupus erythematosus. Oxid Med Cell Longev. 2016;2016:2526174.

[17]

Zeng H, Chi H. Metabolic control of regulatory T cell development and function. Trends Immunol. 2015;36(1):3-12.

[18]

Zhao L, Wu Q, Wang X, et al. Reversal of abnormal CD4+ T cell metabolism alleviates thyroiditis by deactivating the mTOR/HIF1a/glycolysis pathway. Front Endocrinol. 2021;12:659738.

[19]

Chávez MD, Tse HM. Targeting mitochondrial-derived reactive oxygen species in T cell-mediated autoimmune diseases. Front Immunol. 2021;12:703972.

[20]

Li J, Zhao M, Luo W, et al. B cell metabolism in autoimmune diseases: signaling pathways and interventions. Front Immunol. 2023;14:1232820.

[21]

Mandel EM, Grosschedl R. Transcription control of early B cell differentiation. Curr Opin Immunol. 2010;22(2):161-167.

[22]

Raza IGA, Clarke AJ. B cell metabolism and autophagy in autoimmunity. Front Immunol. 2021;12:681105.

[23]

Burrows N, Maxwell PH. Hypoxia and B cells. Exp Cell Res. 2017;356(2):197-203.

[24]

Zhang J, Wu X, Ma J, et al. Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells. Front Immunol. 2022;13:967576.

[25]

Iperi C, Bordron A, Dueymes M, et al. Metabolic program of regulatory B lymphocytes and influence in the control of malignant and autoimmune situations. Front Immunol. 2021;12:735463.

[26]

Abebe EC, Dejenie TA, Ayele TM, et al. The role of regulatory B cells in health and diseases: a systemic review. J Inflamm Res. 2021;14:75-84.

[27]

Wang L, Wu Z, Xia Y, et al. Single-cell profiling guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma. Clin Transl Med. 2022;12(5):e798.

[28]

Ceronie B, Jacobs BM, Baker D, et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018;265(5):1199-1209.

[29]

Wei L, Sun Y, Kong X-F, et al. The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis. BMC Musculoskelet Disord. 2016;17:352.

[30]

Blanco LP, Kaplan MJ. Metabolic alterations of the immune system in the pathogenesis of autoimmune diseases. PLoS Biol. 2023;21(4):e3002084.

[31]

Kurosaki T, Kometani K, Ise W. Memory B cells. Nat Rev Immunol. 2015;15(3):149-159.

[32]

Salazar-Camarena DC, Ortiz-Lazareno PC, Cruz A, et al. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus. 2016;25(6):582-592.

[33]

Bosello S, Youinou P, Daridon C, et al. Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008;35(7):1256-1264.

[34]

Heinzel S, Binh Giang T, Kan A, et al. A Myc-dependent division timer complements a cell-death timer to regulate T cell and B cell responses. Nat Immunol. 2017;18(1):96-103.

[35]

Marchingo JM, Sinclair LV, Howden AJ, et al. Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation. Elife. 2020;9:e53725.

[36]

Maissan P, Mooij EJ, Barberis M. Sirtuins-mediated system-level regulation of mammalian tissues at the interface between metabolism and cell cycle: a systematic review. Biology. 2021;10(3):194.

[37]

Verstegen NJM, Ubels V, Westerhoff HV, et al. System-level scenarios for the elucidation of T cell-mediated germinal center B cell differentiation. Front Immunol. 2021;12:734282.

[38]

Rastogi I, Jeon D, Moseman JE, et al. Role of B cells as antigen presenting cells. Front Immunol. 2022;13:954936.

[39]

Liu Z, Liu S, Zhang Y, et al. Distinct roles of ICOS and CD40L in human T–B cell adhesion and antibody production. Cell Immunol. 2021;368:104420.

[40]

Perl A. Oxidative stress in the pathology and treatment of systemic lupus erythematosus. Nat Rev Rheumatol. 2013; 9(11):674-686.

[41]

Vukelic M, Kono M, Tsokos GC. T cell metabolism in lupus. Immunometabolism. 2020;2(2):e200009.

[42]

Siska PJ, van der Windt GJW, Kishton RJ, et al. Suppression of Glut1 and glucose metabolism by decreased Akt/mTORC1 signalling drives T cell impairment in B cell leukemia. J Immunol. 2016;197(6):2532-2540.

[43]

van Bruggen JAC, van der Windt GJW, Hoogendoorn M, et al. Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells. Blood Adv. 2022;6(14):4185-4195.

[44]

Li R, Tang H, Burns JC, et al. BTK inhibition limits B-cell–T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy. Acta Neuropathol. 2022;143(4):505-521.

[45]

Hamaidi I, Kim S. Sirtuins are crucial regulators of T cell metabolism and functions. Exp Mol Med. 2022;54(3):207-215.

[46]

Xiao F, Rui K, Shi X, et al. Epigenetic regulation of B cells and its role in autoimmune pathogenesis. Cell Mol Immunol. 2022;19(11):1215-1234.

[47]

Mazzone R, Zwergel C, Artico M, et al. The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics. 2019;11(1):34.

[48]

Wang Z, Long H, Chang C, et al. Crosstalk between metabolism and epigenetic modifications in autoimmune diseases: a comprehensive overview. Cell Mol Life Sci. 2018;75(18):3353-3369.

[49]

Sommese L, Benincasa G, Lanza M, et al. Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes. J Diabetes Complications. 2018;32(11):1076-1084.

[50]

Aso K, Kono M, Kanda M, et al. Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming. Nat Commun. 2023;14(1):984.

[51]

Lee K-A, Robbins PD, Camell CD. Intersection of immunometabolism and immunosenescence during ageing. Curr Opin Pharmacol. 2021;57:107-116.

[52]

Barberis M. Quantitative model of eukaryotic Cdk control through the Forkhead CONTROLLER. NPJ Syst Biol Appl. 2021;7(1):28.

[53]

Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B. Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology. 2005;114(1):37-43.

[54]

Dixit VD. Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence. Semin Immunol. 2012;24:321-330.

[55]

Zhao TV, Sato Y, Goronzy JJ, et al. T-cell aging-associated phenotypes in autoimmune disease. Front Aging. 2022;3:867950.

[56]

Frasca D, Romero M, Garcia D, et al. Obesity accelerates age-associated defects in human B cells through a metabolic reprogramming induced by the fatty acid palmitate. Front Aging. 2021;2:828697.

[57]

Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752-1761.

[58]

Teng X, Cornaby C, Li W, et al. Metabolic regulation of pathogenic autoimmunity: therapeutic targeting. Curr Opin Immunol. 2019;61:10-16.

[59]

Sun W, Li P, Cai J, et al. Lipid metabolism: immune regulation and therapeutic prospectives in systemic lupus erythematosus. Front Immunol. 2022;13:860586.

[60]

Young KE, Flaherty S, Woodman KM, et al. Fatty acid synthase regulates the pathogenicity of Th17 cells. J Leukoc Biol. 2017;102(5):1229-1235.

[61]

Piranavan P, Bhamra M, Perl A. Metabolic targets for treatment of autoimmune diseases. Immunometabolism. 2020;2(2):e200012.

[62]

Jia L, Zhang L, Liu M, et al. Mitochondrial control for healthy and autoimmune T cells. Cells. 2023;12(13):1800.

[63]

Das UN. Pro- and anti-inflammatory bioactive lipids imbalance contributes to the pathobiology of autoimmune diseases. Eur J Clin Nutr. 2023;77:637-651.

[64]

Fletcher J, Bishop EL, Harrison SR, et al. Autoimmune disease and interconnections with vitamin D. Endocr Connect. 2022;11(3):e210554.

[65]

Meier-Stephenson FS, Meier-Stephenson VC, Carter MD, et al. Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites. Alzheimers Dement. 2022;8(1):e12283.

RIGHTS & PERMISSIONS

2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics

AI Summary AI Mindmap
PDF

379

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/