Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis

Wang, Xiaohua; Zhang, Jintao; Baylink, David J.; Li, Chih-Huang; Watts, Douglas M.; Xu, Yi; Qin, Xu‐Jie; Walter, Michael H.; Tang, Xiaolei

doi:10.1038/srep36064

Cited by 10 publications

(7 citation statements)

References 81 publications

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“…FACS analysis. FACS analysis was performed as described previously (46,51). Briefly, cells at approximately 5 × 10 6 to 10 × 10 6 cells/ml were first incubated with anti-CD32 antibody (553141, BD Biosciences) at 4 o C for 15 minutes to block Fc receptors before addition of fluorescence-labeled antibodies that stained cell surface proteins.…”

Section: Methodsmentioning

confidence: 99%

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

et al. 2018

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An indispensable role of macrophages in bone repair has been well recognized. Previous data have demonstrated the copresence of M1 macrophages and mesenchymal stem cells (MSCs) during the proinflammatory stage of bone repair. However, the exact role of M1 macrophages in MSC function and bone repair is unknown. This study aimed to define the role of M1 macrophages at bone injury sites via the function of 1,25-Dihydroxyvitamin D (1,25[OH]2D) in suppressing M1 but promoting M2 differentiation. We showed that 1,25(OH)2D suppressed M1 macrophage-mediated enhancement of MSC migration. Additionally, 1,25(OH)2D inhibited M1 macrophage secretion of osteogenic proteins (i.e., Oncostatin M, TNF-α, and IL-6). Importantly, the 1,25(OH)2D-mediated suppression of osteogenic function in M1 macrophages at the proinflammatory stage was associated with 1,25(OH)2D-mediated reduction of MSC abundance, compromised osteogenic potential of MSCs, and impairment of fracture repair. Furthermore, outside the proinflammatory stage, 1,25(OH)2D treatment did not suppress fracture repair. Accordingly, our data support 2 conclusions: (a) M1 macrophages are important for the recruitment and osteogenic priming of MSCs and, hence, are necessary for fracture repair, and (b) under vitamin D-sufficient conditions, 1,25(OH)2D treatment is unnecessary and can be detrimental if provided during the proinflammatory stage of fracture healing.

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Section: Methodsmentioning

confidence: 99%

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

et al. 2018

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“…In addition to classically described CD4 + CD25 + Foxp3 + Treg cells, Foxp3 neg Tr1 cells, regulatory B cells, and CD8 + regulatory T cells may have various roles in regulating different aspects of the autoimmune response in EAE as discussed in Ref. ( 17 – 22 ). The initial observations indicating a role of Treg cells in inhibition of CNS inflammation came from experiments that showed a suppressive cell population arising during the recovery stage of EAE that was able to prevent EAE and suppress T effector cells when transferred into healthy animals ( 23 – 26 ).…”

Section: The Role Of Immune Regulation In Multiple Sclerosis (Ms) Andmentioning

confidence: 96%

Peripherally Induced Regulatory T Cells: Recruited Protectors of the Central Nervous System against Autoimmune Neuroinflammation

Jones

Hawiger

2017

Front. Immunol.

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Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the induction of immune tolerance in the thymus including thymically produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antigens. This review discusses the specific roles of Treg cells in blocking neuroinflammation, examines the impact of peripheral tolerance and dendritic cells on a relevant regulation of neuroinflammation, and explores some of the most recent advances in elucidation of specific mechanisms of the conversion and function of pTreg cells including the roles of CD5 and Hopx in these processes.

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“…47,48 In addition, some Qa-1-restricted CD8 + T cells react with myelinderived peptide antigens. 49 In mice, Qa-1-restricted CD8 + Tregs are induced during treatment with glatiramer acetate, 50 which is a peptide that mimics MBP and an Food and Drug Administrationapproved MS treatment. The disease-ameliorating effects of glatiramer acetate are dependent on Qa-1-restricted CD8 + Tregs.…”

Section: Adaptive Lymphocytesmentioning

confidence: 99%

Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE

et al. 2019

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which the immune system damages the protective insulation surrounding the nerve fibers that project from neurons. A hallmark of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), is autoimmunity against proteins of the myelin sheath. Most studies in this field have focused on the roles of CD4 + T lymphocytes, which form part of the adaptive immune system as both mediators and regulators in disease pathogenesis. Consequently, the treatments for MS often target the inflammatory CD4 + T-cell responses. However, many other lymphocyte subsets contribute to the pathophysiology of MS and EAE, and these subsets include CD8 + T cells and B cells of the adaptive immune system, lymphocytes of the innate immune system such as natural killer cells, and subsets of innate-like T and B lymphocytes such as γδ T cells, natural killer T cells, and mucosal-associated invariant T cells. Several of these lymphocyte subsets can act as mediators of CNS inflammation, whereas others exhibit immunoregulatory functions in disease. Importantly, the efficacy of some MS treatments might be mediated in part by effects on lymphocytes other than CD4 + T cells. Here we review the contributions of distinct subsets of lymphocytes on the pathogenesis of MS and EAE, with an emphasis on lymphocytes other than CD4 + T cells. A better understanding of the distinct lymphocyte subsets that contribute to the pathophysiology of MS and its experimental models will inform the development of novel therapeutic approaches.

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Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis

Cited by 10 publications

References 81 publications

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

Peripherally Induced Regulatory T Cells: Recruited Protectors of the Central Nervous System against Autoimmune Neuroinflammation

Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE

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