EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis

Clottu, Aurélie; Mathias, Amandine; Sailer, Andreas W.; Schluep, Myriam; Pasquier, Renaud Du; Pot, Caroline

doi:10.1016/j.celrep.2016.12.006

Cited by 38 publications

(59 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another theory describes the potential for EBV to preferentially drive proinflammatory B cell cytokine responses [e.g., tumor necrosis factor (TNF), lymphotoxin (LT), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression] [40,41] and interfere with the downregulatory function of IL-10. Another theory based on the ability of EBV to induce expression of EBV-induced G protein-coupled receptor 2 (EBI2/ GPR183) [42][43][44][45] supports, in part, migration of autoreactive T cells and EBV-infected B cells into the CNS.…”

Section: Box 1 Ebv Involvement Across the Ms Spectrummentioning

confidence: 99%

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

Bar‐Or

Pender

Khanna

et al. 2020

Trends in Molecular Medicine

185

135

View full text Add to dashboard Cite

New treatments for multiple sclerosis (MS) focused on B cells have created an atmosphere of excitement in the MS community. B cells are now known to play a major role in disease, demonstrated by the highly impactful effect of a B cell-depleting antibody on controlling MS. The idea that a virus may play a role in the development of MS has a long history and is supported mostly by studies demonstrating a link between B cell-tropic Epstein-Barr virus (EBV) and disease onset. Efforts to develop antiviral strategies for treating MS are underway. Although gaps remain in our understanding of the etiology of MS, the role, if any, of viruses in propagating pathogenic immune responses deserves attention. HighlightsClinical studies show that depletion of B cells reduces disease burden in both relapsing-remitting and progressive multiple sclerosis (MS) patients.

show abstract

Section: Box 1 Ebv Involvement Across the Ms Spectrummentioning

confidence: 99%

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

Bar‐Or

Pender

Khanna

et al. 2020

Trends in Molecular Medicine

185

135

View full text Add to dashboard Cite

show abstract

“…1a) in human peripheral blood mononuclear cells (PBMC). 19 EBI2 expression was also observed in PBMCs without significant differences between healthy volunteers and IBD patients (CD and UC, Fig. 1b).…”

Section: Human Intestinal Lymphocytes Express Ebi2mentioning

confidence: 82%

The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis

et al. 2019

Self Cite

View full text Add to dashboard Cite

The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis. Accordingly, we detected elevated levels of 25-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol in mice with acute colonic inflammation. Knockout of EBI2 or CH25H did not affect severity of DSS colitis; however, inflammation was decreased in male EBI2 −/− mice in the IL-10 colitis model. The colonic immune system comprises mucosal lymphoid structures, which accumulate upon chronic inflammation in IL-10-deficient mice and in chronic DSS colitis. However, EBI2 −/− mice formed significantly less colonic lymphoid structures at baseline and showed defects in inflammation-induced accumulation of lymphoid structures. In summary, we report induction of the EBI2-7α,25dihydroxycholesterol axis in colitis and a role of EBI2 for the accumulation of lymphoid tissue during homeostasis and inflammation. These data implicate the EBI2-7α,25-dihydroxycholesterol axis in IBD pathogenesis.Mucosal Immunology (2019) 12:733-745; https://doi.

show abstract

“…Both oxysterols modulate the immune response, 25-OHC controls viral infection in macrophages ( 1 ) and 7α,25-OH promotes macrophage and B cell trafficking within lymphoid structures ( 2 ). We showed that 7α,25-OHC promotes memory CD4 + T cell migration to the target inflammatory organs during autoimmunity ( 3 , 4 ). While authors have proposed oxysterols as pro-inflammatory mediators, others have submitted 25-OHC as an anti-inflammatory intervener ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production

Vigne¹,

Chalmin

Duc³

et al. 2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

The behaviors of lymphocytes, including CD4+ T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism. The oxysterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC) regulate antiviral immunity and immune cell chemotaxis. However, their physiological effects on adaptive immune response in particular on various subset CD4+ T lymphocytes are largely unknown. Here, we assessed oxysterol levels in subset of CD4+ T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25-hydroxylase, were specifically increased in IL-27-induced type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as a negative regulator of TR1 cells in particular of IL-10 secretion via liver X receptor signaling. Not only do these findings unravel molecular mechanisms accounting for IL-27 signaling but also they highlight oxysterols as pro-inflammatory mediators that dampens regulatory T cell responses and thus unleash a pro-inflammatory response.

show abstract

EBI2 Expression and Function: Robust in Memory Lymphocytes and Increased by Natalizumab in Multiple Sclerosis

Cited by 38 publications

References 33 publications

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

Epstein–Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies

The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis

IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production

Contact Info

Product

Resources

About