Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Ample Evidence ◽

Tfh Cells ◽

Follicular T Helper Cells ◽

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

International Journal of Molecular Sciences ◽

10.3390/ijms19103233 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3233 ◽

Cited By ~ 7

Author(s):

James Quinn ◽

Robert Axtell

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Autoimmune Disorder ◽

T Helper ◽

Ample Evidence ◽

Tfh Cells ◽

Follicular T Helper Cells ◽

Multiple sclerosis (MS) is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and experimental autoimmune encephalomyelitis (EAE). The curation of this literature has identified that central nervous system (CNS) infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Regulatory Role of Peritoneal B Cells in EAE

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2015-0048 ◽

2016 ◽

Vol 17 (2) ◽

pp. 87-92

Author(s):

Bojana Stojanović ◽

Jelena Milovanović ◽

Aleksandar Arsenijević ◽

Marija Milovanovic ◽

Miodrag L. Lukic

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Regulatory Role ◽

Disease Development ◽

Regulatory B Cells ◽

Inflammatory Stimuli ◽

Abstract B cells play a dual role in the pathogenesis of autoimmune diseases. In experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis, B cells contribute to disease progression, while their regulatory role predominates in the initial phases of disease development. Several studies have identified different subsets of regulatory B cells, mostly in the spleen, which are all sources of IL-10. However, peritoneal regulatory B cells are also important producers of IL-10, can migrate towards inflammatory stimuli, and could have an immunoregulatory function. As we have observed expansion of regulatory B cells in the peritoneum of resistant mice after EAE induction, herein we discuss the regulatory roles of B cells in EAE pathogenesis and the possible role of peritoneal regulatory B cells in resistance to EAE induction.

Role of B cells in the development of multiple sclerosis and experimental autoimmune encephalomyelitis

PONS - medicinski casopis ◽

10.5937/pomc10-3867 ◽

2013 ◽

Vol 10 (3) ◽

pp. 109-118

Author(s):

Jovicic Nemanja ◽

Jeftic Ilija ◽

Jovicic Ugljesa

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE

International Journal of Molecular Sciences ◽

10.3390/ijms22062924 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2924

Author(s):

Zahra Maria ◽

Emma Turner ◽

Agnieshka Agasing ◽

Gaurav Kumar ◽

Robert C. Axtell

Keyword(s):

B Cells ◽

B Cell ◽

Pertussis Toxin ◽

Th17 Cells ◽

Experimental System ◽

T Helper ◽

T Cell Infiltration ◽

Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX’s effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.

Potential Role of Humoral Immunity in the Pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)

Frontiers in Bioscience ◽

10.2741/2268 ◽

2007 ◽

Vol 12 (1) ◽

pp. 2735 ◽

Cited By ~ 18

Author(s):

Maria del Pilar Martin

Keyword(s):

Multiple Sclerosis ◽

Humoral Immunity ◽

Potential Role ◽

Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

Clinical and Developmental Immunology ◽

10.1155/2013/968549 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 75

Author(s):

Ning Qu ◽

Mingli Xu ◽

Izuru Mizoguchi ◽

Jun-ichi Furusawa ◽

Kotaro Kaneko ◽

...

Keyword(s):

Th17 Cell ◽

Th17 Cells ◽

Functional Role ◽

Inflammatory Diseases ◽

Interleukin 17 ◽

T Helper ◽

T Helper 17 ◽

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

The Role of Toll-Like Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Multiple Sclerosis Immunology ◽

10.1007/978-1-4614-7953-6_8 ◽

2013 ◽

pp. 149-176

Author(s):

Bruno Gran ◽

Mukanthu H. Nyirenda ◽

James Crooks

Keyword(s):

Multiple Sclerosis ◽

Toll Like Receptors ◽

The Immune-Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Clinical and Developmental Immunology ◽

10.1155/2010/186813 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 31

Author(s):

Hong-Liang Zhang ◽

Jiang Wu ◽

Jie Zhu

Keyword(s):

Multiple Sclerosis ◽

Apolipoprotein E ◽

T Cell Proliferation ◽

Special Focus ◽

Multiple Functions ◽

Lipid Antigen ◽

Apolipoprotein E (apoE) is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT) cells, and so forth. Increasing studies have revealed that APOEεallele might be associated with multiple sclerosis (MS), although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOEεallele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE).

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217317690184 ◽

2017 ◽

Vol 3 (1) ◽

pp. 205521731769018 ◽

Cited By ~ 3

Author(s):

Bert A ’t Hart ◽

Yolanda S Kap

Keyword(s):

B Cells ◽

Epstein Barr Virus ◽

Infection Prevalence ◽

Barr Virus ◽

Experimental Autoimmune Encephalomyelitis Model ◽

Epstein Barr ◽

Infection with Epstein–Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60–90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV–MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein.