Biological Characteristics of Transcription Factor RelB in Different Immune Cell Types: Implications for the Treatment of Multiple Sclerosis

Overview

Journal Mol Brain

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2019 Dec 29

PMID 31881915

Citations 14

Authors

Meng-Ge Yang

Li Sun

Jinming Han

Chao Zheng

Hudong Liang

Jie Zhu

Tao Jin

Affiliations

Soon will be listed here.

Abstract

Transcription factor RelB is a member of the nuclear factror-kappa B (NF-κB) family, which plays a crucial role in mediating immune responses. Plenty of studies have demonstrated that RelB actively contributes to lymphoid organ development, dendritic cells maturation and function and T cells differentiation, as well as B cell development and survival. RelB deficiency may cause a variety of immunological disorders in both mice and humans. Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system which involves a board of immune cell populations. Thereby, RelB may exert an impact on MS by modulating the functions of dendritic cells and the differentiation of T cells and B cells. Despite intensive research, the role of RelB in MS and its animal model, experimental autoimmune encephalomyelitis, is still unclear. Herein, we give an overview of the biological characters of RelB, summarize the updated knowledge regarding the role of RelB in different cell types that contribute to MS pathogenesis and discuss the potential RelB-targeted therapeutic implications for MS.

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References

Tegowski M, Baldwin A . Noncanonical NF-κB in Cancer. Biomedicines. 2018; 6(2). PMC: 6027307. DOI: 10.3390/biomedicines6020066. View

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

Milo R, Miller A . Revised diagnostic criteria of multiple sclerosis. Autoimmun Rev. 2014; 13(4-5):518-24. DOI: 10.1016/j.autrev.2014.01.012. View

Tan H, Wang N, Man K, Tsao S, Che C, Feng Y . Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin. Cell Death Dis. 2015; 6:e1942. PMC: 4632300. DOI: 10.1038/cddis.2015.271. View

Ulzheimer J, Meuth S, Bittner S, Kleinschnitz C, Kieseier B, Wiendl H . Therapeutic approaches to multiple sclerosis: an update on failed, interrupted, or inconclusive trials of immunomodulatory treatment strategies. BioDrugs. 2010; 24(4):249-74. DOI: 10.2165/11537160-000000000-00000. View

Wu H, Lo Y, Chan A, Law K, Mok M . Rel B-modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro. Immunology. 2016; 149(1):48-61. PMC: 4981611. DOI: 10.1111/imm.12628. View

Seki T, Yamamoto M, Taguchi Y, Miyauchi M, Akiyama N, Yamaguchi N . Visualization of RelB expression and activation at the single-cell level during dendritic cell maturation in Relb-Venus knock-in mice. J Biochem. 2015; 158(6):485-95. DOI: 10.1093/jb/mvv064. View

Mazzola M, Raheja R, Regev K, Beynon V, von Glehn F, Paul A . Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells. Mult Scler. 2017; 25(1):63-71. DOI: 10.1177/1352458517740213. View

Josefowicz S, Lu L, Rudensky A . Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012; 30:531-64. PMC: 6066374. DOI: 10.1146/annurev.immunol.25.022106.141623. View

10.

Fletcher J, Lalor S, Sweeney C, Tubridy N, Mills K . T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010; 162(1):1-11. PMC: 2990924. DOI: 10.1111/j.1365-2249.2010.04143.x. View

11.

Bours V, Azarenko V, Dejardin E, Siebenlist U . Human RelB (I-Rel) functions as a kappa B site-dependent transactivating member of the family of Rel-related proteins. Oncogene. 1994; 9(6):1699-702. View

12.

Palle P, Monaghan K, Milne S, Wan E . Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications. Med Sci (Basel). 2017; 5(4). PMC: 5753652. DOI: 10.3390/medsci5040023. View

13.

Matusevicius D, Kivisakk P, He B, Kostulas N, Ozenci V, Fredrikson S . Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler. 1999; 5(2):101-4. DOI: 10.1177/135245859900500206. View

14.

Morrison M, Reiley W, Zhang M, Sun S . An atypical tumor necrosis factor (TNF) receptor-associated factor-binding motif of B cell-activating factor belonging to the TNF family (BAFF) receptor mediates induction of the noncanonical NF-kappaB signaling pathway. J Biol Chem. 2005; 280(11):10018-24. DOI: 10.1074/jbc.M413634200. View

15.

McGinley A, Edwards S, Raverdeau M, Mills K . Th17 cells, γδ T cells and their interplay in EAE and multiple sclerosis. J Autoimmun. 2018; . DOI: 10.1016/j.jaut.2018.01.001. View

16.

Vaknin-Dembinsky A, Balashov K, Weiner H . IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol. 2006; 176(12):7768-74. DOI: 10.4049/jimmunol.176.12.7768. View

17.

Dohler A, Schneider T, Eckert I, Ribechini E, Andreas N, Riemann M . RelB Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3 Regulatory T Cells. Front Immunol. 2017; 8:726. PMC: 5479892. DOI: 10.3389/fimmu.2017.00726. View

18.

Powolny-Budnicka I, Riemann M, Tanzer S, Schmid R, Hehlgans T, Weih F . RelA and RelB transcription factors in distinct thymocyte populations control lymphotoxin-dependent interleukin-17 production in γδ T cells. Immunity. 2011; 34(3):364-74. DOI: 10.1016/j.immuni.2011.02.019. View

19.

Petermann F, Rothhammer V, Claussen M, Haas J, Blanco L, Heink S . γδ T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism. Immunity. 2010; 33(3):351-63. PMC: 3008772. DOI: 10.1016/j.immuni.2010.08.013. View

20.

Weih D, Yilmaz Z, Weih F . Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol. 2001; 167(4):1909-19. DOI: 10.4049/jimmunol.167.4.1909. View