NKT cells: manipulable managers of joint inflammation

Coppieters, Ken; Dewint, Pieter; Beneden, Katrien Van; Jacques, Peggy; Seeuws, Sylvie; Verbruggen, Gust; Deforce, Dieter; Elewaut, Dirk

doi:10.1093/rheumatology/kel437

Cited by 31 publications

(22 citation statements)

References 78 publications

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“…Several studies have provided evidence for a pathogenic role of NKT cells in CIA (reviewed in [122]). One group of investigators showed that blockade of the interaction between CD1d and NKT cells with anti-CD1d antibodies resulted in reduced arthritis [123].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Natural Killer T Cells and Autoimmune Disease

Kaer²

2009

CMM

157

159

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Natural killer T (NKT) cells are an unusual subset of innate immune cells that express a surface receptor generated by somatic DNA rearrangement, a hallmark of cells of the adaptive immune system. NKT cells express a highly restricted repertoire of T cell receptors that recognize glycolipid antigens bound with the antigen-presenting molecule CD1d. A hallmark of NKT cells is their capacity to produce copious amounts of immunomodulatory cytokines upon antigenic stimulation, which endows these cells with potent immunoregulatory properties. Consequently, NKT cells have been implicated in regulating a wide variety of immune responses, including immune responses against autoantigens. In patients and mice with a variety of autoimmune diseases, numbers and functions of NKT cells are disturbed, but the relevance of these findings to the etiology of autoimmunity remains to be fully established. Nevertheless, in some mouse models of autoimmunity, NKT cell-deficiency exacerbates disease, suggesting that NKT cells play a role in suppressing autoimmunity. Conversely, specific activation of NKT cells with glycolipid antigens generally protects mice against the development of autoimmunity. Most of these studies have employed the potent sponge-derived NKT cell antigen alpha-galactosylceramide (alpha-GalCer). However, alpha-GalCer treatment in mice was associated with detrimental side effects and treatment efficacy was influenced by a variety of parameters, resulting sometimes in disease exacerbation rather than protection. Recent efforts have focused on developing NKT cell agonists with superior treatment efficacy than alpha-GalCer. Collectively, these studies have identified NKT cells as attractive targets for treatment of human autoimmune diseases.

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Section: Rheumatoid Arthritismentioning

confidence: 99%

Natural Killer T Cells and Autoimmune Disease

Kaer²

2009

CMM

157

159

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“…The most commonly used animal model for RA, is induced by immunization of susceptible mouse strains with heterologous type-II collagen (CIA). Several studies suggest that NKT cells play a pathogenic role in CIA [75]. Studies performed with different mouse models for RA, have demonstrated that NKT play two opposite roles in arthritis, probably due to functional differences between type I NKT and type II NKT cells.…”

Section: Other Autoimmune Diseasesmentioning

confidence: 99%

“…Studies performed with different mouse models for RA, have demonstrated that NKT play two opposite roles in arthritis, probably due to functional differences between type I NKT and type II NKT cells. In fact type II NKT suppress arthritis while type I NKT cells play a pathogenic role in this disease [75][76][77][78]. Systemic lupus erythematosus (SLE) is mediated by autoantibodies directed against nuclear antigens a process controlled by autoreactive T helper cells and regulatory T cells.…”

Section: Other Autoimmune Diseasesmentioning

confidence: 99%

Dissecting the Roles of Natural Killer T cells in Autoimmune Disorders and Malignancy

Bimonte¹,

Antonio²,

Palma³

et al. 2013

J Clin Cell Immunol

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Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer (NK) cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and non-self glycolipids and lipids. NKT cells are able to influence autoimmune and cancer diseases, thanks to their innate and adaptative immune properties. A hallmark of NKT cells is their ability to express proand anti-inflammatory T helper(h)1 and Th2 cytokines upon antigenic stimulation, and to modify both inflammatory mediators and late stage T cell responses. Thus, NKT cells are considered critical cells in regulatory events that direct the inflammatory response. Additionally, NKT cells can regulate the functions of other NKT subsets. The purpose of this review is to highlight the importance of NKT cells as regulators of autoimmunity disorders and cancer.

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“…A series of studies have indicated that iNKT cells play an aggravating role in mouse models of inflammatory arthritis (reviewed in [118]). iNKT cell numbers were increased in liver and peripheral blood after induction of CIA and in the K/BxN arthritis model [119].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Invariant Natural Killer T Cell-Based Therapy of Autoimmune Diseases

Gabriel¹,

Wu²,

Parekh³

et al. 2010

CIR

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Invariant natural killer T (iNKT) cells are a unique subset of T lymphocytes that share characteristics with both innate and adaptive immune cells. The iNKT cell receptor recognizes glycolipid antigens presented in the context of CD1d, an analogue of the major histocompatibility complex class I molecule. These cells rapidly produce a variety of cytokines in response to stimuli, providing them with the capacity to regulate the activities of other cells in the immune system. These regulatory properties of iNKT cells play critical roles in a variety of disease models for infection, autoimmunity, inflammation and cancer. Here, we review the role of iNKT cells in modulating the immune response in autoimmune diseases and we discuss prospects and limitations for targeting iNKT cells during immunotherapy for these diseases.

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NKT cells: manipulable managers of joint inflammation

Cited by 31 publications

References 78 publications

Natural Killer T Cells and Autoimmune Disease

Natural Killer T Cells and Autoimmune Disease

Dissecting the Roles of Natural Killer T cells in Autoimmune Disorders and Malignancy

Invariant Natural Killer T Cell-Based Therapy of Autoimmune Diseases

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