The potential role of iNKT cells in experimental allergic encephalitis and multiple sclerosis

Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56bright NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56dim NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway. Aim We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes. Materials and Methods The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease‐modifying therapies on the number of NK and NKT subtypes. Results Expansion of CD56bright NK cells, reduction in the CD56dim cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease‐modifying therapies. Conclusion Expansion of CD56bright NK cells or reduction in the CD56dim cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow.

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“…Hence, these cells play an immunoregulatory role in autoimmune diseases (Figure 2 ). 71 , 74 , 75 , 76 …”

Section: Natural Killer T Cellsmentioning

confidence: 99%

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

Ahmadi

Vastani

Abounoori

et al. 2022

Health Science Reports

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“…To further profile immune mediators able to modulate the RANKL/RANK/OPG axis, we selected IL-4, IL-10, IL-17, CCL2, and CXCL12, suggested to play a role in MS pathogenesis [26][27][28].…”

Section: Profile Of Inflammatory Mediators In the Pbl And Csf Of Ms Pmentioning

confidence: 99%

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

Glasnović

Stojić

Dežmalj

et al. 2018

Neuroimmunomodulation

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Objectives: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. Results: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. Conclusion: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

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“…7 cells are a unique population of T lymphocytes with the capacity to impact a wide array of functions of the immune system, ranging from protection against infections to responses to tumors and the regulation of autoimmunity (1,2). These cells accomplish this feat through their ability to secrete T helper type 1 (Th1) and T helper type 2 (Th2) cytokines, most notably IFN-␥ and IL-4, respectively, and their ability to impact other white blood cells, such as natural killer cells, dendritic cells, and B cells (3)(4)(5).…”

Section: Natural Killer T (Nkt)mentioning

confidence: 99%

Lipid and Carbohydrate Modifications of α-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation

Birkholz

Nemčovič

et al. 2015

Journal of Biological Chemistry

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Background:Several synthetic glycosphingolipids have been tested to determine their capacity to activate type I NKT cells. Results: Although the TCR binds with high affinity to all CD1d-presented glycolipids, only a few activate type I NKT cells in vivo. Conclusion: TCR binding affinity does not necessarily predict antigenicity in vivo.Significance: The prediction of the therapeutic efficacy of type I NKT cell antigens requires complementary assays.

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The potential role of iNKT cells in experimental allergic encephalitis and multiple sclerosis

Cited by 11 publications

References 124 publications

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

Lipid and Carbohydrate Modifications of α-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation

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