Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity

Cho, Young Nan; Kee, Seung‐Jung; Lee, Sung Ji; Seo, Seong Rye; Kim, Tae Jong; Lee, Shin Seok; Kim, Min Soo; Lee, Won Woo; Yoo, Dae Hyun; Kim, Nacksung; Park, Yong Wook

doi:10.1093/rheumatology/keq457

Cited by 76 publications

(103 citation statements)

References 37 publications

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“…Numerical deficiencies of immune cells in the peripheral blood have often been linked to functional deficiencies of these cells in autoimmune diseases (17,40). Because the same abnormalities might exist in MAIT cells of SLE and RA patients, we considered performing functional studies that assess the relationship between FIGURE 5.…”

Section: Discussionmentioning

confidence: 99%

“…MAIT cells and NKT cells were identified phenotypically as CD3 + TCRgd 2 Va7.2 + CD161 high and CD3 + 6B11 + cells, respectively, by flow cytometry as previously described (4,5,17,19). To confirm whether the reported proportions of MAIT cells in PBMCs contain the MAIT cell rearrangement, we performed TCR genotyping in sorted CD3 + TCRgd 2 Va7.2 + CD161 high cells.…”

Section: Isolation Of Pbmcs and The Identification Of Mait And Nkt Cellsmentioning

confidence: 99%

“…Therefore, NKT cells have been implicated in the control of autoimmune diseases, cancer, and infectious diseases (16). Our previous studies and those by other groups have demonstrated numerical and functional deficiencies of NKT cells in autoimmune diseases (17)(18)(19)(20). Although MAIT and NKT cells exclusively share the expression of the transcription factor PZLF (ZBTB16), emphasizing a close lineage relationship between these two distinct subsets, MAIT cell ontogeny is clearly different from NKT cells (5,21,22).…”

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confidence: 93%

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Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Cho

Kee

Kim

et al. 2014

The Journal of Immunology

150

163

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Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8+ and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide–stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.

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Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Pbmcs and The Identification Of Mait And Nkt Cellsmentioning

confidence: 99%

mentioning

confidence: 93%

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Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Cho

Kee

Kim

et al. 2014

The Journal of Immunology

150

163

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“…Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation using Ficoll-Paque Plus solution (Amersham Bioscience, Uppsala, Sweden), and monocytes and T cells were purified from PBMCs by magnetically activated cell sorting (MACS) as previously described (9,36). NKT cells were identified phenotypically as CD3 ϩ 6B11 ϩ cells by flow cytometry (3,9,16,34,43). NKT cell proliferation assays.…”

Section: Methodsmentioning

confidence: 99%

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

et al. 2012

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d Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis infection. The aims of this study were to examine NKT cell levels and functions in patients with active M. tuberculosis infection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to ␣-galactosylceramide (␣-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to ␣-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to ␣-GalCer in M. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably, M. tuberculosis infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to ␣-GalCer. This study shows that NKT cell levels and functions are reduced in M. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.

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“…Reduced numbers of NKT cells are observed in the peripheral blood of patients with SLE, and NKT cell deficiency is inversely correlated with disease activity. In addition, proliferation and cytokine production are impaired (77)(78)(79).…”

Section: Increased Production Of Il-17mentioning

confidence: 99%

T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity

Moulton¹,

Tsokos²

2015

J. Clin. Invest.

196

147

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Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity

Abstract: Our data show that NKT cell levels and functions are defective in SLE patients. Furthermore, these deficiencies were found to reflect disease activity. It would appear that these NKT cell abnormalities could contribute to immune system dysregulation in SLE.

Cited by 76 publications

References 37 publications

Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus

Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection

T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity

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