PD-1/PD-L1 Axis As a Potential Therapeutic Target for Multiple Sclerosis: A T Cell Perspective

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2021 Aug 12

PMID 34381337

Citations 10

Authors

Haixia Li

Chao Zheng

Jinming Han

Jie Zhu

Shan Liu

Tao Jin

Affiliations

Soon will be listed here.

Abstract

The programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1) axis is a widely studied immune checkpoint that modulates signaling pathways related to T cell activation. The use of PD-1/PD-L1 inhibitors is a promising immune therapy strategy for cancer patients. However, individuals treated with PD-1/PD-L1 inhibitors may develop immune-related adverse events due to excessive immune reactions. Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system. T cells and the PD-1/PD-L1 axis play vital roles in the pathogenesis of MS. A better understanding of the complex relationship between the PD-1/PD-L1 axis and T cells may extend our knowledge of the molecular mechanisms and therapeutic approaches for MS. In this review, we summarize the most recent findings regarding the role of the PD-1/PD-L1 axis in MS and discuss the potential therapeutic strategies to modulate the expression of PD-1/PD-L1 in MS.

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References

Saidu N, Kavian N, Leroy K, Jacob C, Nicco C, Batteux F . Dimethyl fumarate, a two-edged drug: Current status and future directions. Med Res Rev. 2019; 39(5):1923-1952. DOI: 10.1002/med.21567. View

Good-Jacobson K, Song E, Anderson S, Sharpe A, Shlomchik M . CD80 expression on B cells regulates murine T follicular helper development, germinal center B cell survival, and plasma cell generation. J Immunol. 2012; 188(9):4217-25. PMC: 3331930. DOI: 10.4049/jimmunol.1102885. View

Garcia K, Adams J, Feng D, Ely L . The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat Immunol. 2009; 10(2):143-7. PMC: 3982143. DOI: 10.1038/ni.f.219. View

Bommarito D, Hall C, Taams L, Corrigall V . Inflammatory cytokines compromise programmed cell death-1 (PD-1)-mediated T cell suppression in inflammatory arthritis through up-regulation of soluble PD-1. Clin Exp Immunol. 2017; 188(3):455-466. PMC: 5422858. DOI: 10.1111/cei.12949. View

Zare-Shahabadi A, Renaudineau Y, Rezaei N . MicroRNAs and multiple sclerosis: from physiopathology toward therapy. Expert Opin Ther Targets. 2013; 17(12):1497-507. DOI: 10.1517/14728222.2013.838219. View

Yang M, Sun L, Han J, Zheng C, Liang H, Zhu J . Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis. Mol Brain. 2019; 12(1):115. PMC: 6935142. DOI: 10.1186/s13041-019-0532-6. View

Kurebayashi Y, Nagai S, Ikejiri A, Ohtani M, Ichiyama K, Baba Y . PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORγ. Cell Rep. 2012; 1(4):360-73. DOI: 10.1016/j.celrep.2012.02.007. View

Lee G . The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci. 2018; 19(3). PMC: 5877591. DOI: 10.3390/ijms19030730. View

Patsoukis N, Sari D, Boussiotis V . PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A. Cell Cycle. 2012; 11(23):4305-9. PMC: 3552912. DOI: 10.4161/cc.22135. View

10.

Esensten J, Helou Y, Chopra G, Weiss A, Bluestone J . CD28 Costimulation: From Mechanism to Therapy. Immunity. 2016; 44(5):973-88. PMC: 4932896. DOI: 10.1016/j.immuni.2016.04.020. View

11.

Ferrajoli A, Shanafelt T, Ivan C, Shimizu M, Rabe K, Nouraee N . Prognostic value of miR-155 in individuals with monoclonal B-cell lymphocytosis and patients with B chronic lymphocytic leukemia. Blood. 2013; 122(11):1891-9. PMC: 3779381. DOI: 10.1182/blood-2013-01-478222. View

12.

Dobson R, Giovannoni G . Multiple sclerosis - a review. Eur J Neurol. 2018; 26(1):27-40. DOI: 10.1111/ene.13819. View

13.

Blackburn S, Shin H, Nicholas Haining W, Zou T, Workman C, Polley A . Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2008; 10(1):29-37. PMC: 2605166. DOI: 10.1038/ni.1679. View

14.

Glatigny S, Bettelli E . Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS). Cold Spring Harb Perspect Med. 2018; 8(11). PMC: 6211376. DOI: 10.1101/cshperspect.a028977. View

15.

Ciotti J, Cross A . Disease-Modifying Treatment in Progressive Multiple Sclerosis. Curr Treat Options Neurol. 2018; 20(5):12. DOI: 10.1007/s11940-018-0496-3. View

16.

Dong H, Strome S, Matteson E, Moder K, Flies D, Zhu G . Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J Clin Invest. 2003; 111(3):363-70. PMC: 151851. DOI: 10.1172/JCI16015. View

17.

Seifert H, Gerstner G, Kent G, Vandenbark A, Offner H . Estrogen-induced compensatory mechanisms protect IL-10-deficient mice from developing EAE. J Neuroinflammation. 2019; 16(1):195. PMC: 6821034. DOI: 10.1186/s12974-019-1588-z. View

18.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

19.

Shimizu K, Sugiura D, Okazaki I, Maruhashi T, Takegami Y, Cheng C . PD-1 Imposes Qualitative Control of Cellular Transcriptomes in Response to T Cell Activation. Mol Cell. 2020; 77(5):937-950.e6. DOI: 10.1016/j.molcel.2019.12.012. View

20.

Wiesemann E, Deb M, Trebst C, Hemmer B, Stangel M, Windhagen A . Effects of interferon-beta on co-signaling molecules: upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis. Mult Scler. 2007; 14(2):166-76. DOI: 10.1177/1352458507081342. View