scholarly journals Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261727
Author(s):  
Chien-Ya Hsu ◽  
Yu-Shan Chueh ◽  
Ming-Ling Kuo ◽  
Pei-Tzu Lee ◽  
Hsiu-Shan Hsiao ◽  
...  

CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observed that 1. The percentages of Vα24+/Vβ11+ iNKT cells following 10-day incubation was lower in SLE groups compared to controls; 2. The percentages and absolute numbers of Vα24+/Vβ11+ iNKT cells were expanded by α-galactosylceramide (α-Galcer), and further enhanced with IL-15 in SLE patient, but the effect of IL-15 was much lower than controls; 3.IL-15 +α-Galcer expanded CD3+/CD56+ NKT-like cells from SLE patients, especially with active disease 4. The CD161+ Vα24+/Vβ11+ iNKT cells in SLE were more responsive to α-Galcer stimulation than the CD161- counterpart; 5. IL-15 decreased apoptosis of α-Galcer activated SLE iNKT cells; 6. IL-15 enhanced CD69, CD1d and CD11a expression on α-Galcer treated iNKT cells; 7. The IL-4 production of iNKT cells was decreased in SLE patients compared to controls; 8. IL-15 increased IFN-γ and IL-4 production of SLE iNKT cells; 8. IL-15 failed to augment the ability of iNKT cells to aid NK-mediated K562 cytolysis in SLE patients; 9. CD161 positivity, granzyme B and perforin expression of α-Galcer+IL-15 expanded iNKT cells correlated with C3 levels in SLE patients. Taken together, our results demonstrated numeric and functional deficiency of iNKT cells and their response to IL-15 in SLE patients. Our finding may provide insight for using adoptive iNKT cell therapy in autoimmune diseases.

2006 ◽  
Vol 56 (1) ◽  
pp. 303-310 ◽  
Author(s):  
Matthew R. J. Green ◽  
Amy S. M. Kennell ◽  
Maggie J. Larche ◽  
Martin H. Seifert ◽  
David A. Isenberg ◽  
...  

2013 ◽  
Vol 71 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Silke C. Hofmann ◽  
Anneleen Bosma ◽  
Leena Bruckner-Tuderman ◽  
Milica Vukmanovic-Stejic ◽  
Elizabeth C. Jury ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Ping Chuang ◽  
Chih-Hung Wang ◽  
Ning-Chi Wang ◽  
Deh-Ming Chang ◽  
Huey-Kang Sytwu

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with complex immunological and clinical manifestations. Multiple organ failure in SLE can be caused by immune dysfunction and deposition of autoantibodies. Studies of SLE-susceptible loci and the cellular and humoral immune responses reveal variable aberrations associated with this systemic disease. Invariant natural killer T (iNKT) cells are a unique subset of lymphocytes that control peripheral tolerance. Mounting evidence showing reductions in the proportion and activity of iNKT cells in SLE patients suggests the suppressive role of iNKT cells. Studies using murine lupus models demonstrate that iNKT cells participate in SLE progression by sensing apoptotic cells, regulating immunoglobulin production, and altering the cytokine profile upon activation. However, the dichotomy of iNKT cell actions in murine models implies complicated interactions within the body's milieu. Therefore, application of potential therapy for SLE using glycolipids to regulate iNKT cells should be undertaken cautiously.


Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3491-3500 ◽  
Author(s):  
Dominik Schneidawind ◽  
Jeanette Baker ◽  
Antonio Pierini ◽  
Corina Buechele ◽  
Richard H. Luong ◽  
...  

Key Points Low doses of adoptively transferred third-party CD4+ iNKT cells protect from lethal GVHD while preserving graft-versus-tumor effects. Third-party CD4+ iNKT cells are rejected early after transplantation yet protect from GVHD lethality through donor Tregs.


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