CD38: T Cell Immuno-Metabolic Modulator

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Jul 26

PMID 32709019

Citations 36

Authors

Anwesha Kar

Shikhar Mehrotra

Shilpak Chatterjee

Affiliations

Soon will be listed here.

Abstract

Activation and subsequent differentiation of T cells following antigenic stimulation are triggered by highly coordinated signaling events that lead to instilling cells with a discrete metabolic and transcriptional feature. Compelling studies indicate that intracellular nicotinamide adenine dinucleotide (NAD) levels have profound influence on diverse signaling and metabolic pathways of T cells, and hence dictate their functional fate. CD38, a major mammalian NAD glycohydrolase (NADase), expresses on T cells following activation and appears to be an essential modulator of intracellular NAD levels. The enzymatic activity of CD38 in the process of generating the second messenger cADPR utilizes intracellular NAD and thus limits its availability to different NAD consuming enzymes (PARP, ART, and sirtuins) inside the cells. The present review discusses how the CD38-NAD axis affects T cell activation and differentiation through interfering with their signaling and metabolic processes. We also describe the pivotal role of the CD38-NAD axis in influencing the chromatin remodeling and rewiring T cell response. Overall, this review emphasizes the crucial contribution of the CD38NAD axis in altering T cell response in various pathophysiological conditions.

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References

Camacho-Pereira J, Tarrago M, Chini C, Nin V, Escande C, Warner G . CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016; 23(6):1127-1139. PMC: 4911708. DOI: 10.1016/j.cmet.2016.05.006. View

Harnick D, Jayaraman T, Ma Y, Mulieri P, Go L, Marks A . The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation. J Biol Chem. 1995; 270(6):2833-40. DOI: 10.1074/jbc.270.6.2833. View

Tang B . Sirt1 and the Mitochondria. Mol Cells. 2016; 39(2):87-95. PMC: 4757807. DOI: 10.14348/molcells.2016.2318. View

de Weers M, Tai Y, van der Veer M, Bakker J, Vink T, Jacobs D . Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2010; 186(3):1840-8. DOI: 10.4049/jimmunol.1003032. View

Kwong A, Chen Z, Zhang H, Leung F, Lam C, Ting K . Catalysis-based inhibitors of the calcium signaling function of CD38. Biochemistry. 2011; 51(1):555-64. DOI: 10.1021/bi201509f. View

Viegas M, do Carmo A, Silva T, Seco F, Serra V, Lacerda M . CD38 plays a role in effective containment of mycobacteria within granulomata and polarization of Th1 immune responses against Mycobacterium avium. Microbes Infect. 2007; 9(7):847-54. DOI: 10.1016/j.micinf.2007.03.003. View

Klein-Hessling S, Muhammad K, Klein M, Pusch T, Rudolf R, Floter J . NFATc1 controls the cytotoxicity of CD8 T cells. Nat Commun. 2017; 8(1):511. PMC: 5593830. DOI: 10.1038/s41467-017-00612-6. View

Chen Y, Zander R, Khatun A, Schauder D, Cui W . Transcriptional and Epigenetic Regulation of Effector and Memory CD8 T Cell Differentiation. Front Immunol. 2018; 9:2826. PMC: 6292868. DOI: 10.3389/fimmu.2018.02826. View

Gao Z, Ye J . Inhibition of transcriptional activity of c-JUN by SIRT1. Biochem Biophys Res Commun. 2008; 376(4):793-6. PMC: 2629791. DOI: 10.1016/j.bbrc.2008.09.079. View

10.

Curtsinger J, Mescher M . Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol. 2010; 22(3):333-40. PMC: 2891062. DOI: 10.1016/j.coi.2010.02.013. View

11.

Feng X, Zhang L, Acharya C, An G, Wen K, Qiu L . Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma. Clin Cancer Res. 2017; 23(15):4290-4300. PMC: 5540790. DOI: 10.1158/1078-0432.CCR-16-3192. View

12.

Kietzmann T, Petry A, Shvetsova A, Gerhold J, Gorlach A . The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol. 2017; 174(12):1533-1554. PMC: 5446579. DOI: 10.1111/bph.13792. View

13.

Malavasi F, Funaro A, Alessio M, DeMonte L, Ausiello C, Dianzani U . CD38: a multi-lineage cell activation molecule with a split personality. Int J Clin Lab Res. 1992; 22(2):73-80. DOI: 10.1007/BF02591400. View

14.

Nimmagadda V, Bever C, Vattikunta N, Talat S, Ahmad V, Nagalla N . Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets. J Immunol. 2013; 190(9):4595-607. PMC: 3963275. DOI: 10.4049/jimmunol.1202584. View

15.

Thevarajan I, Nguyen T, Koutsakos M, Druce J, Caly L, van de Sandt C . Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020; 26(4):453-455. PMC: 7095036. DOI: 10.1038/s41591-020-0819-2. View

16.

van Loosdregt J, Brunen D, Fleskens V, Pals C, Lam E, Coffer P . Rapid temporal control of Foxp3 protein degradation by sirtuin-1. PLoS One. 2011; 6(4):e19047. PMC: 3080399. DOI: 10.1371/journal.pone.0019047. View

17.

Rifai K, Judes G, Idrissou M, Daures M, Bignon Y, Penault-Llorca F . SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer. Oncotarget. 2018; 9(55):30661-30678. PMC: 6078139. DOI: 10.18632/oncotarget.25771. View

18.

Chen L, Flies D . Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013; 13(4):227-42. PMC: 3786574. DOI: 10.1038/nri3405. View

19.

Bono M, Fernandez D, Flores-Santibanez F, Rosemblatt M, Sauma D . CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression. FEBS Lett. 2015; 589(22):3454-60. DOI: 10.1016/j.febslet.2015.07.027. View

20.

Iino M, Endo M . Calcium-dependent immediate feedback control of inositol 1,4,5-triphosphate-induced Ca2+ release. Nature. 1992; 360(6399):76-8. DOI: 10.1038/360076a0. View