The Effect of α-Galactosylceramide, Specific Antigen for iNKT Cells, on Cytokine Profiles in BALB/c Mice
Keywords:
iNKT cells; α-GalCer; BALB/c mice; cytokine kinetic; IFN-γ, หนูสายพันธุ์ BALB/c; การเปลี่ยนแปลงของไซโตไคน์Abstract
Background and Objective: Invariant natural killer T (iNKT) cells are T cells subset that can secrete various cytokines respond to lipid or glycolipid antigens presented by CD1d on antigen presenting cells. α-Galactosylceramide (α-GalCer), the specific antigen for iNKT cells, can activate iNKT cells to secrete both proinflammatory and regulatory cytokines to activate the other immune cells. This study aimed to investigate the kinetic of cytokines in BALB/c mice at several time points after α-GalCer injection.
Methods: BALB/c mice were intraperitoneal injected with 1µg of α-GalCer per mouse and collected the blood samples at time points 1, 2, 4, 6, 12 and 24 hours post-injection. The samples were determined the cytokine levels by Cytometric Bead Array.
Results: GM-CSF, IFN-γ and IL-4 were the major cytokines detected in high levels in the early time point. IFN-γ was the highest cytokine levels. IL-10, IL-13 and IL-17A were low levels at the early time points and increased at the late time points. However, the levels were not high when compared to major cytokines.
Conclusions: The consequence after single dose injection of α-GalCer in BALB/c mice showed the cytokines kinetic in each time-point and IFN-γ was the highest detectable cytokine. From the cytokine kinetic studied, this experiment is an alternative model could be used as data for the α-GalCer experimental design in various diseases.
References
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28. O'Brien TF, Bao K, Dell'Aringa M, Ang WX, Abraham S, Reinhardt RL. Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation. Mucosal Immunol 2016; 9: 597-609.
29. Wingender G, Rogers P, Batzer G, Lee MS, Bai D, Pei B, et al. Invariant NKT cells are required for airway inflammation induced by environmental antigens. J Exp Med 2011; 208: 1151-62.
30. Michel ML, Keller AC, Paget C, Fujio M, Trottein F, Savage PB, et al. Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med 2007; 204: 995-1001.
2. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol 2007; 25: 297-336.
3. Van Kaer L, Parekh VV, Wu L. Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res 2011; 343: 43-55.
4. Gadola SD, Koch M, Marles-Wright J, Lissin NM, Shepherd D, Matulis G, et al. Structure and binding kinetics of three different human CD1d-alpha-galactosylceramide-specific T cell receptors. J Exp Med 2006; 203: 699-710.
5. Cantu C, 3rd, Benlagha K, Savage PB, Bendelac A, Teyton L. The paradox of immune molecular recognition of alpha-galactosylceramide: low affinity, low specificity for CD1d, high affinity for alpha beta TCRs. J Immunol 2003; 170: 4673-82.
6. Matsuda JL, Mallevaey T, Scott-Browne J, Gapin L. CD1d-restricted iNKT cells, the 'Swiss-Army knife' of the immune system. Curr Opin Immunol 2008; 20: 358-68.
7. Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 2002; 13: 413-21.
8. Skold M, Behar SM. Role of CD1d-restricted NKT cells in microbial immunity. Infect Immun 2003; 71: 5447-55.
9. Kinjo Y, Kitano N, Kronenberg M. The role of invariant natural killer T cells in microbial immunity. J Infect Chemother 2013; 19: 560-70.
10. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 2005; 23: 877-900.
11. Rymarchyk SL, Lowenstein H, Mayette J, Foster SR, Damby DE, Howe IW, et al. Widespread natural variation in murine natural killer T-cell number and function. Immunology 2008; 125: 331-43.
12. Sada-Ovalle I, Skold M, Tian T, Besra GS, Behar SM. Alpha-galactosylceramide as a therapeutic agent for pulmonary Mycobacterium tuberculosis infection. Am J Respir Crit Care Med 2010; 182: 841-7.
13. Emoto M, Yoshida T, Fukuda T, Kawamura I, Mitsuyama M, Kita E, et al. Alpha-galactosylceramide promotes killing of Listeria monocytogenes within the macrophage phagosome through invariant NKT-cell activation. Infect Immun 2010; 78: 2667-76.
14. Matsuda JL, Gapin L, Baron JL, Sidobre S, Stetson DB, Mohrs M, et al. Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci U S A 2003; 100: 8395-400.
15. Zhang Y, Springfield R, Chen S, Li X, Feng X, Moshirian R, et al. alpha-GalCer and iNKT Cell-Based Cancer Immunotherapy: Realizing the Therapeutic Potentials. Front Immunol 2019; 10: 1126.
16. Cao Z, Dhupar R, Cai C, Li P, Billiar TR, Geller DA. A critical role for IFN regulatory factor 1 in NKT cell-mediated liver injury induced by alpha-galactosylceramide. J Immunol 2010; 185: 2536-43.
17. Parekh VV, Wilson MT, Olivares-Villagomez D, Singh AK, Wu L, Wang CR, et al. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J Clin Invest 2005; 115: 2572-83.
18. Kim S, Lalani S, Parekh VV, Vincent TL, Wu L, Van Kaer L. Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J Clin Invest 2008; 118: 2301-15.
19. Fujii S, Shimizu K, Kronenberg M, Steinman RM. Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol 2002; 3: 867-74.
20. Wen X, Rao P, Carreno LJ, Kim S, Lawrenczyk A, Porcelli SA, et al. Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells. Proc Natl Acad Sci U S A 2013; 110: 2963-8.
21. Bai L, Constantinides MG, Thomas SY, Reboulet R, Meng F, Koentgen F, et al. Distinct APCs explain the cytokine bias of alpha-galactosylceramide variants in vivo. J Immunol 2012; 188: 3053-61.
22. Sag D, Ozkan M, Kronenberg M, Wingender G. Improved Detection of Cytokines Produced by Invariant NKT Cells. Sci Rep 2017; 7: 16607.
23. Chackerian A, Alt J, Perera V, Behar SM. Activation of NKT cells protects mice from tuberculosis. Infect Immun 2002; 70: 6302-9.
24. Rothchild AC, Jayaraman P, Nunes-Alves C, Behar SM. iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS Pathog 2014; 10: e1003805.
25. Tessmer MS, Fatima A, Paget C, Trottein F, Brossay L. NKT cell immune responses to viral infection. Expert Opin Ther Targets 2009; 13: 153-62.
26. Diana J, Lehuen A. NKT cells: friend or foe during viral infections? Eur J Immunol 2009; 39: 3283-91.
27. McKnight CG, Morris SC, Perkins C, Zhu Z, Hildeman DA, Bendelac A, et al. NKT cells contribute to basal IL-4 production but are not required to induce experimental asthma. PLoS One 2017; 12: e0188221.
28. O'Brien TF, Bao K, Dell'Aringa M, Ang WX, Abraham S, Reinhardt RL. Cytokine expression by invariant natural killer T cells is tightly regulated throughout development and settings of type-2 inflammation. Mucosal Immunol 2016; 9: 597-609.
29. Wingender G, Rogers P, Batzer G, Lee MS, Bai D, Pei B, et al. Invariant NKT cells are required for airway inflammation induced by environmental antigens. J Exp Med 2011; 208: 1151-62.
30. Michel ML, Keller AC, Paget C, Fujio M, Trottein F, Savage PB, et al. Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med 2007; 204: 995-1001.
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2019-11-13
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Kasetthat T, W. Sermswan R, Watarai H, Wongratanacheewin S. The Effect of α-Galactosylceramide, Specific Antigen for iNKT Cells, on Cytokine Profiles in BALB/c Mice. SRIMEDJ [Internet]. 2019 Nov. 13 [cited 2024 Apr. 19];34(6):602-7. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/225141
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