Activation of Invariant Natural Killer T Cell Subsets in C57BL/6J Mice by Different Injection Modes of α-galactosylceramide
-
Ming Meng
,
Shengde Chen
,
Xiang Gao
,
Huifang Liu
,
Huijuan Zhao
,
Jingnan Zhang
,
Jinku Zhang
,
Dongzhi Chen
Abstract
Whether different injection modes of α-galactosylceramide (α-GalCer) affect the activation of different subsets of invariant natural killer T (iNKT) cells in different tissues and organs of mice is unclear. This study included healthy control, subcutaneous injection, and intraperitoneal injection groups (n=10 in each group). The subcutaneous and intraperitoneal injection groups were injected with α-Galcer (0.1 mg/kg weight), and then the changes in thymus, spleen, and liver iNKT cell frequencies and subsets were observed. The intraperitoneal injection of α-GalCer could increase the frequency of splenic iNKT cells, but the subcutaneous injection did not affect the frequency. Neither injection had any effect on the frequency of iNKT cells in the thymus and liver. The subcutaneous injection of α-GalCer increased the rate of iNKT2 subsets in the thymus but did not affect the rate of iNKT1 subsets. However, the intraperitoneal injection of α-GalCer did not affect thymus iNKT1 and iNKT2 subsets. Interestingly, the subcutaneous injection of α-GalCer significantly increased the proportion of iNKT1 in the spleen and liver but did not significantly change the proportion of iNKT2. The intraperitoneal injection of α-GalCer significantly increased the rate of iNKT2 in spleen and liver but decreased the rate of iNKT1. Subsets of iNKT1 or iNKT2 cells in the spleen and liver were selectively activated by the subcutaneous or intraperitoneal injection of α-GalCer. It provides a valuable means for treating tumors and certain autoimmune diseases. Further exploration of the activation mechanism may provide new ideas about the development of related vaccines.
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27. Scanlon ST, Thomas SY, Ferreira CM, Bai L, Krausz T, Savage PB, et al. Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation. J Exp Med 2011; 208(10):2113-24.
28. Constantinides MG, Bendelac A. Transcriptional regulation of the NKT cell lineage. Curr Opin Immunol 2013; 25(2):161–7.
29. Kwon DI, Lee YJ. Lineage Differentiation Program of Invariant Natural Killer T Cells. Immune Netw 2017; 17(6):365-77.
30. Doisne JM, Becourt C, Amniai L, Duarte N, Le Luduec JB, Eberl G, et al. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions. J Immunol 2009; 183(3):2142-9.
31. Gapin L. Development of invariant natural killer T cells. Curr Opin Immunol 2016; 39:68-74.
32.Kim EY, Lynch L, Brennan PJ, Cohen NR, Brenner MB. The transcriptional programs of iNKT cells. Semin Immunol 2015; 27(1):26-32.
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34. Chen D, Gao X, Wang J, Zhao H, Liu H, Chen S, et al. Activation of hepatic iNKT2 cells by alpha-GalCer ameliorates hepatic steatosis induced by high-fat diet in C57BL/6J mice. Int Immunopharmacol 2019; 74:105727.
35. Chen D, Liu H, Wang Y, Chen S, Liu J, Li W, et al. Study of the adoptive immunotherapy on rheumatoid arthritis with Thymus-derived invariant natural killer T cells. Int Immunopharmacol. 2019; 67:427-40.
36. CHEN D, WANG Y, ZHANG X, LIU J, YANG F, YIN X, et al. Effects of an immunostimulator CH 2 b on Th1/Th2 and Th17/Treg immune imbalance in RA mice. Chin J Microbiol Immunol 2017; 37(2):97-104.
37. Meng M, YANG F, Xu M, Chen D, Hou M, Liu J, et al. Effects of a novel synthetic immunostimulator CH2b on iNKT cells isolated from patients with active rheumatoid arthritis. Chin J Microbiol Immunol 2015; 35(12):916-20.
38. MENG M, WANG Z, LI C, HAN H, SHI J, CHEN H, et al. A novel synthetic immunostimulator CH1a containing thiazolidin-4-one enhances the function of human iNKT cells in vitro. Chin J Microbiol Immunol 2013; 33(6):452-7.
2. Beckman EM, Porcelli SA, Morita CT, Behar SM, Furlong ST, Brenner MB. Recognition of a lipid antigen by CD1-restricted αβ+T cells. Nature 1994; 372(6507):691–4.
3. Godfrey DI, Hammond KJL, Poulton LD, Smyth MJ, Baxter AG. NKT cells: facts, functions and fallacies. Immunol Today 2000; 21(11):573-83.
4. Brossay L CM, Burdin N, Koezuka Y, Casorati G, Dellabona P, Kronenberg M. CD1d-mediated recognition of anα-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 1998; 188(8):1521–8.
5. Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T, et al. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med 2003; 9(5):582-8.
6. Sakuishi K, Oki S, Araki M, Porcelli SA, Miyake S, Yamamura T. Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. J Immunol 2007; 179(6):3452-62.
7. Cerundolo V, Silk JD, Masri SH, Salio M. Harnessing invariant NKT cells in vaccination strategies. Nat Rev Immunol 2009; 9(1):28-38.
8. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol 2007; 25:297-336.
9. Hegde S, Chen X, Keaton JM, Reddington F, et al. NKT cells direct monocytes into a DC differentiation pathway. J Leukoc Biol 2007; 81(5):1224-35.
10. Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, et al. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 2003; 171(10):5140-7.
11. Bennstein SB. Unraveling Natural Killer T-Cells Development. Front Immunol 2017; 8:1950.
12. Lee YJ, Wang H, Starrett GJ, Phuong V, Jameson SC, Hogquist KA. Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response. Immunity 2015; 43(3):566-78.
13. White AJ, Lucas B, Jenkinson WE, Anderson G. Invariant NKT Cells and Control of the Thymus Medulla. J Immunol 2018; 200(10):3333-9.
14. Cameron G, Godfrey DI. Differential surface phenotype and context-dependent reactivity of functionally diverse NKT cells. Immunol Cell Biol 2018.
15. Kawano T CJ, Koezuka Y, Toura I, Kaneko Y, Motoki K, Ueno H, Nakagawa R, Sato H, Kondo E, Koseki H, Taniguchi M. CD1d restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 1997; 278(5343):1626–9.
16. Horikoshi M, Goto D, Segawa S, Yoshiga Y, Iwanami K, Inoue A, et al. Activation of Invariant NKT cells with glycolipid ligand alpha-galactosylceramide ameliorates glucose-6-phosphate isomerase peptide-induced arthritis. PLoS One 2012; 7(12):e51215.
17. Kinjo, Y., Takatsuka, S., Kitano, N., Kawakubo, S., Abe, M., Ueno, K., et al. Functions of CD1d-Restricted Invariant Natural Killer T Cells in Antimicrobial Immunity and Potential Applications for Infection Control. Front Immunol. 2018;9:1266.
18. Yang JQ, Kim PJ, Singh RR. Brief treatment with iNKT cell ligand alpha-galactosylceramide confers a long-term protection against lupus. J Clin Immunol 2012; 32(1):106-13.
19. Vahedi G, Kanno Y, Furumoto Y, Jiang K, Parker SC, Erdos MR, et al. Super-enhancers delineate disease-associated regulatory nodes in T cells. Nature 2015; 520(7548):558-62.
20. 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(3):358-68.
21. Miyamoto K, Miyake S, Yamamura T. A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Nature 2001; 413(6855):531–4.
22. Yu KOA, Im JS, Molano A, Dutronc Y, Illarionov PA, Forestier C, Fujiwara N, Arias I, Miyake S, Yamamura T, Chang YT, Besra GS, Porcelli SA. Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of α-galactosylceramides. Proc Natl Acad Sci USA 2005; 102(9):3383–8.
23. 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(7):3053-61.
24. Zhang H, Xue R, Zhu S, Fu S, Chen Z, Zhou R, et al. M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue. Cell Mol Immunol 2018; 15(5):506-17.
25. Thomas SY, Scanlon ST, Griewank KG, Constantinides MG, Savage AK, Barr KA, et al. PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions. J Exp Med 2011; 208(6):1179-88.
26. Lynch L, Michelet X, Zhang S, Brennan PJ, Moseman A, Lester C, et al. Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol 2015; 16(1):85-95.
27. Scanlon ST, Thomas SY, Ferreira CM, Bai L, Krausz T, Savage PB, et al. Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation. J Exp Med 2011; 208(10):2113-24.
28. Constantinides MG, Bendelac A. Transcriptional regulation of the NKT cell lineage. Curr Opin Immunol 2013; 25(2):161–7.
29. Kwon DI, Lee YJ. Lineage Differentiation Program of Invariant Natural Killer T Cells. Immune Netw 2017; 17(6):365-77.
30. Doisne JM, Becourt C, Amniai L, Duarte N, Le Luduec JB, Eberl G, et al. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions. J Immunol 2009; 183(3):2142-9.
31. Gapin L. Development of invariant natural killer T cells. Curr Opin Immunol 2016; 39:68-74.
32.Kim EY, Lynch L, Brennan PJ, Cohen NR, Brenner MB. The transcriptional programs of iNKT cells. Semin Immunol 2015; 27(1):26-32.
33.Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 2013; 13(2):101-17.
34. Chen D, Gao X, Wang J, Zhao H, Liu H, Chen S, et al. Activation of hepatic iNKT2 cells by alpha-GalCer ameliorates hepatic steatosis induced by high-fat diet in C57BL/6J mice. Int Immunopharmacol 2019; 74:105727.
35. Chen D, Liu H, Wang Y, Chen S, Liu J, Li W, et al. Study of the adoptive immunotherapy on rheumatoid arthritis with Thymus-derived invariant natural killer T cells. Int Immunopharmacol. 2019; 67:427-40.
36. CHEN D, WANG Y, ZHANG X, LIU J, YANG F, YIN X, et al. Effects of an immunostimulator CH 2 b on Th1/Th2 and Th17/Treg immune imbalance in RA mice. Chin J Microbiol Immunol 2017; 37(2):97-104.
37. Meng M, YANG F, Xu M, Chen D, Hou M, Liu J, et al. Effects of a novel synthetic immunostimulator CH2b on iNKT cells isolated from patients with active rheumatoid arthritis. Chin J Microbiol Immunol 2015; 35(12):916-20.
38. MENG M, WANG Z, LI C, HAN H, SHI J, CHEN H, et al. A novel synthetic immunostimulator CH1a containing thiazolidin-4-one enhances the function of human iNKT cells in vitro. Chin J Microbiol Immunol 2013; 33(6):452-7.
| Files | ||
| Issue | Vol 19, No 1 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v19i1.2416 | |
| PMID | 32245319 | |
| Keywords | ||
| Cytokines Invariant natural killer T cells Intraperitoneal injection Subcutaneous injection α-galactosylceramide | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Meng M, Chen S, Gao X, Liu H, Zhao H, Zhang J, Zhang J, Chen D. Activation of Invariant Natural Killer T Cell Subsets in C57BL/6J Mice by Different Injection Modes of α-galactosylceramide. Iran J Allergy Asthma Immunol. 2020;19(1):35-44.
