Involvement of iNKT Cells In Bronchial Asthma


  • Swarnima Kandari Department of Pharmacy practice, SGRRITS, Dehradun, India
  • Ratnakar . Department of Pharmacy practice, SGRRITS, Dehradun, India
  • Abhishek Chandola Department of Pharmacy practice, SGRRITS, Dehradun, India



asthma, glycolipid ligand, iNKT cells, Th2 cytokine, airway hypersensitivity, α-galactosylceramide


Background: Bronchial asthma is a prevalent inflammatory disease characterized by infiltration with eosinophils, lymphocytes, and mast cells in the airway leading to airway hypersensitivity and increased mucus secretion. T helper (Th) 2-based immune responses drive the inflammatory process. Numerous mechanisms are being studied to understand the progression of allergen induce asthma which subsequently led to the identification of a new population of T cells called the iNKT cells which showed promising results when experimented on murine models.  iNKT cells are potent immune modulators involved in a variety of immunoregulations. This potency is the result of their ability to produce prime Th2 cytokines. The recognition of lipid antigens is required for the activation of iNKT cells. When an inflammation occurs due to Th2 cells and ozone, endogenous glycolipids become modified. This causes the activation of various subsets of iNKT cells and initiates airway hyperactivity. Infrequent human studies depict that the number of iNKT cells in BAL fluid ranges from 1 % of lung lymphocytes to 14 % which is a sign of dynamic fluctuation in the number of iNKT cells.

Methods: Selective literature review including primary and secondary sources of literature. Eg. Cochrane database, NCBI, MEDLINE database.



Download data is not yet available.

Author Biographies

Swarnima Kandari, Department of Pharmacy practice, SGRRITS, Dehradun, India

Department of Pharmacy practice, SGRRITS, Dehradun, India

Ratnakar ., Department of Pharmacy practice, SGRRITS, Dehradun, India

Department of Pharmacy practice, SGRRITS, Dehradun, India

Abhishek Chandola, Department of Pharmacy practice, SGRRITS, Dehradun, India

Department of Pharmacy practice, SGRRITS, Dehradun, India


1. Matangkasombut P, Marigowda G, Ervine A, Idris, L., Pichavant, M., Kim, H. et al. Natural killer T cells in the lungs of patients with asthma. J Allergy Clin Immunol 2009; 123(5):1181-1185. DOI:10.1016/j.jaci.2009.02.013
2. Umetsu D, McIntire J, Akbari O, Macaubas C, DeKruyff R. Asthma: an epidemic of dysregulated immunity. Nat Immunol 2002; 3,715–720. DOI:10.1038/ni0802-715
3. BusseWW, Lemanske RF. Advances in immunology: asthma. N. Engl. J. Med 2001; 344:350–62. DOI:10.1056/nejm200102013440507
4. Victor, J.R, Lezmi, G, Leite-de-Moraes. New Insights into Asthma Inflammation: Focus on iNKT, MAIT, and γδT Cells. Clinic Rev Allerg Immunol 2020; 59, 371–381. DOI:10.1007/s12016-020-08784-8
5. Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127(2):355–360. DOI:10.1016/ j.jaci.2010.11.037
6. Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: moving toward precision medicine. J Allergy Clinical Immunol 2019; 144(1):1–12. DOI:10.1016/j.jaci.2019.05.031
7. Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, et al. After asthma: redefining airways diseases. Lancet 2018; 391(10118):350–400. DOI:10.1016/S0140-6736 (17) 30879-6
8. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006; 368(9537):804–813. DOI:10.1016/S0140- 6736(06)69290-8 6
9. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 2008;372:1107-19. DOI:10.1016/S0140-6736(08)61452-X
10. Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, et al. GINA 2019: a fundamental change in asthma management: treatment of asthma with short acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J 2019;53(6). DOI:10.1183/ 13993003.01046-2019
11. DeKruyff R, Umetsu D, Pichavant M, Akbari O, Yasumi T, Savage P, et al. Activation of nonclassical CD1d-restricted NK T cells induces airway hyperreactivity in beta 2-microglobulin-deficient mice. J Immunol 2008;181(7):4560-4569. DOI:10.4049/jimmunol.181.7.4560
12. Le´tuve´ S, Kadoch S, Audusseau S, Rothenberg ME, Fiset PO, Ludwig MS, IL-17E up regulates the expression of proinflammatory cytokines in lung fibroblasts. J Allergy Clin Immunol 2006; 117(3):590-6. DOI:10.1016/j.jaci.2005.10.025
13. Papotto PH, Ribot JC, Silva-Santos B. IL-17 + γδ T cells as kick-starters of inflammation. Nat Immunol 2017;18(6):604–611. DOI:10.1038/ni.3726
14. Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, et al. A critical role for eosinophils in allergic airways remodelling. Science 2004;305:1776-9. DOI:10.1126/science.1100283
15. Nocker RE, Schoonbrood DF, van de Graaf EA, Hack CE, Lutter R, Jansen HM, et al. Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 1996;109:183-91. DOI:10.1159/000237218
16. Yousefi S, Hemmann S, Weber M, Holzer C, Hartung K, Blaser K, et al. IL-8 is expressed by human peripheral blood eosinophils: evidence for increased secretion in asthma. J Immunol 1995;154:5481-90. DOI:10.3389/fimmu.2014.00570
17. Sears MR, Greene JM, Willan AR, Wiecek E, Taylor D.R, Flannery E.M, et al. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N. Engl. J. Med 2003;349:1414–22. DOI:10.1056/NEJMoa022363
18. Brusasco V, Crimi E, Pellegrino R. Airway hyperresponsiveness in asthma: not just a matter of airway inflammation. Thorax 1998;53(11):992-998. DOI:10.1136/thx.53.11.992
19. Durham SR, Craddock CF, Cookson WO, Benson MK, et al. Increases of airway responsiveness to histamine precede allergen induced late asthmatic responses. J Allergy Clin Immunol 1988; 82:764–70. DOI:10.1016/0091-6749(88)90077-2
20. Rossi GA, Crimi E, Lantero S, Gianiorio P, Oddera S, Crimi P, et al. The late-phase asthmatic reaction to inhaled allergen is associated with an early recruitment of eosinophils in the airways. Am Rev Respir Dis 1991;143:379–83. DOI:10.1164/ajrccm/144.2.379
21. Kava T. Acute respiratory infections, influenza vaccination and airway reactivity in asthma. Eur J Respir Dis 1987; 70(Suppl 150):7–38.
22. Martinez DF. Viral infections and the development of asthma. Am J Respir Crit Care Med 1995; 151:1644–8. DOI:10.1164/ajrccm/151.5_Pt_1.1644
23. Grunberg K, Smits HH, Timmers MC, Klerk EP, Dolhain RJ, Dick EC, et al. Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects. Am J Respir Crit Care Med 1997;158:609–16. DOI:10.1164/ajrccm.156.2.9610079
24. 21. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma From Bronchoconstriction to Airways Inflammation and Remodelling. Am J Respir Crit Care Med. 2000; 161(5):1720-45. DOI:10.1164/ajrccm.161.5.9903102
25. Liu MC, Hubbard WC, Proud D, Stealey BA, Galli SJ, Sobotka AK, et al. Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics: cellular, mediator, and permeability changes. Am. Rev. Respir. Dis 1991;144(1):51–58. DOI:10.1164/ajrccm/144.1.51
26. Tonnel Ab, Joseph M, Gosset P, Fournier E, Capron A. Alveolar Macrophage And Its Participation In The Inflammatory Processes Of Allergic Asthma. Lancet 1986;22 Suppl 7:70-7.
27. Gounni AS, Lamkhioued B, Ochiai K, Tanaka Y, Delaporte E, Capron A, et al. High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature 1994;367: 183–186. DOI:10.1038/367183a0.
28. Greiff L, Erjefalt I, Svensson C, Wollmer P, Alkner U, Andersson M, et al. Plasma exudation and solute absorption across the airway mucosa. Clin. Physiol 1993;13:219–233. DOI:10.1111/j.1475-097X.1993.tb00322.x
29. Georas SN, Liu MC, Newman W, Beall LD, Stealey BA, Bochner BS. Altered adhesion molecule expression and endothelial cell activation accompany the recruitment of human granulocytes to the lung after segmental antigen challenge. Am. J. Respir. Cell Mol. Biol 1992;7(3):261–269. DOI:10.1165/ajrcmb/7.3.261.
30. Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR. Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am. J. Respir. Cell Mol. Biol 1993;8(1):35–42. DOI:10.1165/ajrcmb/8.1.35
31. Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J. Allergy Clin. Immunol 1987;79:734–740. DOI:10.1016/0091-6749(87)90204-1
32. Granger DN, Kubes P. The microcirculation and inflammation: modulation of leukocyte–endothelial cell adhesion. J. Leukoc. Biol 1994;55(5):662–675.
33. Bochner B, Schleimer R. The role of adhesion molecules in human eosinophil and basophil recruitment. J. Allergy Clin. Immunol 1994;94:427–439. DOI:10.1016/0091-6749(94)90195-3
34. Matangkasombut P, Pichavant M, DeKruyff RH, Umetsu DT. Natural killer T cells and the regulation of asthma. Mucosal Immunol. 2009;2(5):383-92. DOI:10.1038/mi.2009.96
35. 35.Ronchi F, Falcone M. Immune regulation by invariant NKT cells in autoimmunity . Front. Biosci 2008; 13:4827 – 4837. DOI:10.2741/3042
36. Rhijn IV , Koets AP, Jin IS, Piebes D, Reddington F, Besra GS, et al. The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d. J. Immunol 2006; 176(8):4888 – 4893. DOI:10.4049/jimmunol.176.8.4888
37. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K, et al. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 1997;278(5343):1626-9. DOI:10.1126/science.278.5343.1626
38. Thomas SY, Lilly CM, Luster AD. Invariant natural killer T cells in bronchial asthma . N. Engl. J. Med. 2006; 354(24):2613-6; author reply 2613-6. DOI:10.1056/nejmc066189
39. Umetsu DT, DeKruyff RH. Opinion—a role for natural killer T cells in asthma. Nat. Rev. Immunol 2006; 6(12):953-8. DOI:10.1038/nri1968
40. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Kaer LV. NKT cells: What’s in a name? Nat. Rev. Immunol 2004;4(3):231–7. DOI:10.1038/nri1309
41. Lisbonne M, Diem S, Keller AD, Lefort J, Araujo LM, Hachem P, et al. Cutting edge: Invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model. J. Immunol 2003; 171(4):1637-41. DOI:10.4049/jimmunol.171.4.1637
42. 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. DOI:10.1038/nm851
43. 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):101–117. DOI:10.1038/ nri3369.
44. Hinks TS, Zhou X, Staples KJ, Dimitrov BD, Manta A, Petrossian T, et al. Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms. J Allergy Clin Immunol 2015;136(2):323–333. DOI:10.1016/j. jaci.2015.01.014
45. Kim CH, Butcher EC, Johnston B. Distinct subsets of human V alpha 24-invariant NKT cells: cytokine responses and chemokine receptor expression. Trends Immunol 2002; 23:516–19. DOI:10.1016/s1471-4906(02)02323-2
46. Gumperz JE, Miyake S, Yamamura T, Brenner MB. Functionally distinct subsets of CD1drestricted natural killer T cells revealed by CD1d tetramer staining. J. Exp. Med 2002; 195:625– 36. DOI:10.1084/jem.20011786
47. Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG, Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med. 2005;202(9):1279-1288. DOI:10.1084/jem.20050953
48. Umetsu DT, DeKruyff RH. Immune dysregulation in asthma. Curr. Opin. Immunol 2006; 18:727–32. DOI:10.1016/j.coi.2006.09.007
49. Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, et al. Requirement for V14 NKT cells in IL-12-mediated rejection of tumors. Science 1997; 278:1623–1626. DOI:10.1126/science.278.5343.1623
50. Michel M., 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(5):995-1001. DOI:10.1084/jem.20061551
51. Liu Y, Goff RD, Zhou D, Mattner J, Sullivan BA, Khurana A, et al. A modified alpha-galactosyl ceramide for staining and stimulating Natural Killer T cells. J. Immunol. Methods 2006; 312:34–39. DOI:10.1016/j.jim.2006.02.009
52. Kim CH, Butcher EC, Johnston B. Distinct subsets of human Vα24-invariant NKT cells: cytokine responses and chemokine receptor expression. Trends Immunol. 2002;23(11):516-9. DOI:10.1016/s1471-4906(02)02323-2
53. Tumes D, Hirahara K, Papadopoulos M, Shinoda K, Onodera A, Kumagai J, et al. Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology. J Allergy Clin Immunol 2019;144(2):549-560.e510. DOI:10.1016/j. jaci.2019.02.024.
54. Lee PT , Benlagha K, Teyton L, Bendelac A. Distinct functional lineages of human Vα24 natural killer T cells. J. Exp. Med.2002; 195(5):637-41. DOI:10.1084/jem.20011908
55. Takahashi T, Chiba S, Nieda M, Azuma T, Ishihara S, Shibata Y, Takeo Juji et al. Analysis of human Vα24+CD8+ NKT cells activated by α-glycosylceramide-pulsed monocyte-derived dendritic cells.J.Immunol.2002;168(7):3140-4.
56. Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR, Brutkiewicz RR. CD1 recognition by mouse NK1 T lymphocytes. Science 1995; 268(5212):863-5. DOI:10.1126/science.7538697
57. Exley M, Garcia J, Balk SP, Porcelli S. Requirements for CD1d recognition by human invariant V 24CD4CD8 T cells. J. Exp. Med. 1997;186:109–120. DOI:10.1084/jem.186.1.109
58. Chandra S, Zhao M, Budelsky A, de Mingo PA, Day J, Fu Z, et al. A new mouse strain for the analysis of invariant NKT cell function. Nat Immunol 2015;16(8):799–800. DOI:10.1038/ni.3203.
59. Pietro CD , FalconeM. The role of invariant NKT cells in organ-specific autoimmunity. Front Biosci (Landmark Ed). 2014;19:1240-50. DOI:10.2741/4279
60. Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA, McKenzie BS, et al. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4- NK1.1.- NKT cell population. Proc Natl Acad Sci U S A 2008;105(32):11287-92. DOI:10.1073/pnas.0801631105
61. ZhouD, Mattner J, Cantu C, Schrantz N, Yin N, Gao Y, et al. Lysosomal glycosphingolipid recognition by NKT cells . Science 2004; 306(5702):1786-9. DOI:10.1126/science.1103440
62. Rauch J, Gumperz J, Robinson C, Sköld M, Roy C, Young DC, et al. Structural features of the acyl chain determine self phospholipid antigen recognition by a CD1d-restricted invariant NKT (iNKT) cell . J. Biol. Chem. 2003; 278(48):47508-15. DOI:10.1074/jbc.m308089200
63. Wu DY, Segal NH, Sidobre S, Kronenberg M, Chapman PB. Cross-presentation of disialoganglioside GD3 to natural killer T cells. J. Exp. Med. 2003; 198(1):173-81. DOI:10.1084/jem.20030446
64. Meyer EH, Goya S, Akbari O, Berry GJ, Savage PB, Kronenberg M,et al. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyper reactivity independent of conventional CD4+ T cells . Proc. Natl. Acad. Sci. USA 2006; 103(8):2782-7. DOI:10.1073/pnas.0510282103
65. Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD, et al. Recognition of bacterial glycosphingolipids by natural killer T cells . Nature 2005; 434(7032):520-5. DOI:10.1038/nature03407
66. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 2005; 434(7032):525-9. DOI:10.1038/nature03408
67. Tsuji, M. Glycolipids and phospholipids as natural CD1d-binding NKT cell ligands. Cell. Mol. Life Sci. 2006; 63(16):1889-98. DOI:10.1007/s00018-006-6073-z
68. Kinjo Y, Tupin E, Wu D, Fujio M, Navarro RG, Benhnia MI, et al. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat. Immunol. 2006; 7(9):978-86. DOI:10.1038/ni1380
69. Pniewska E, Pawliczak R, "The Involvement of Phospholipases A2 in Asthma and Chronic Obstructive Pulmonary Disease", Mediators of Inflammation, vol. 2013. DOI:10.1155/2013/793505.
70. Porubsky S, Speak AO, Luckow B, Cerundolo V, Platt FM, Gröne HJ. Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency. Proc Natl Acad Sci U S A 2007; 104(14):5977-82. DOI:10.1073/pnas.0611139104
71. Moody D, Porcelli S. Intracellular pathways of CD1 antigen presentation. Nat Rev Immunol 2003; 3(1):11-22. DOI:10.1038/nri979
72. Nagarajan N, Kronenberg M. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol. 2007; 178(5):2706-13. DOI:10.4049/jimmunol.178.5.2706
73. Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation du. ring microbial infection. Nat. Immunol. 2003; 4(12):1230-7. DOI:10.1038/ni1002
74. Zhang Y, Springfield R, Chen S, Li X, Feng X, Moshirian R, et al. α-GalCer and iNKT Cell-Based Cancer Immunotherapy: Realizing the Therapeutic Potentials. Front Immunol, 2019; 10:1126. DOI:10.3389/fimmu.2019.01126
75. Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H. The regulatory role of V alpha14 NKT cells in innate and acquired immune
response. Annu. Rev. Immunol. 2003; 21:483-513. DOI:10.1146/annurev.immunol.21.120601.141057
76. Sullivan BA, Kronenberg M. Activation or anergy: NKT cells are stunned by alpha-galactosylceramide. J Clin Invest 2005; 115(9):2328-9. DOI:10.1172/jci26297
77. Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, et al. The natural killer T (NKT) cell ligand galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J. Exp. Med. 1999; 189(7):1121-8. DOI:10.1084/jem.189.7.1121
78. Cohen NR, Garg S, Brenner MB. Antigen presentation by CD1 lipids, T cells, and NKT cells in microbial immunity. Adv Immunol 2009;102:1-94. DOI:10.1016/s0065-2776(09)01201-2
79. Spinozzi F, Porcelli SA. Recognition of lipids from pollens by CD1-restricted T cells. Immunol. Allergy Clin. North Am.2007; 27(1):79-92. DOI:10.1016/j.iac.2006.11.004
80. Pham-Thi N, Blic J, Bourgeois M, Dy M, Scheinmann P, Leite-de-Moraes M. Enhanced frequency of immunoregulatory invariant natural killer T cells in the airways of children with asthma. J. Allergy Clin. Immunol. 2006;117(1):217-8. DOI:10.1016/j.jaci.2005.09.052
81. Hamzaoui A, Cheik Rouhou S, Graïri H, Abid H, Ammar J, Chelbi H, Hamzaoui K. NKT cells in the induced sputum of severe asthmatics. Mediators Inflamm. 2006; 2006(2):71214. DOI:10.1155/MI/2006/71214
82. Sen Y, Yongyi B, Yuling H, Luokun X, Li H, Jie X,et al. Vα24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement. J. Immunol. 2005; 175 (8) 4914-4926. DOI:10.4049/jimmunol.175.8.4914
83. Kim EY, Battaile JT, Patel AC, You Y, Agapov E, Grayson MH, et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease . Nat. Med. 2008; 14(6):633-40. DOI:10.1038/nm1770
84. Matangkasombut P, Marigowda G, Ervine A, Idris L, Pichavant M, Kim HY, et al. Natural killer T cells in the lungs of patients with asthma . J. Allergy Clin. Immunol. 2009; 123(5):1181-5. DOI:10.1016/j.jaci.2009.02.013
85. Mutalithas K, Croudace J, Guillen C, Siddiqui S, Thickett D, Wardlaw A, et al. Bronchoalveolar lavage invariant natural killer T cells are not increased in asthma . J. Allergy Clin. Immunol. 2007; 119(5):1274-6. DOI:10.1016/j.jaci.2007.02.021
86. Vijayanand P, Seumois G, Pickard C, Powell RM, Angco G, Sammut D, et al. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease . N. Engl. J. Med. 2007; 356(14):1410-22. DOI:10.1056/NEJMoa064691
87. Pichavant M, Goya S, Meyer EH, Johnston RA, Kim HY, Matangkasombut P, et al. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J Exp Med 2008; 205(2):385-93. DOI:10.1084/jem.20071507
88. Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, et al. CD4+ invariant T-cell-receptor1 natural killer T cells in bronchial asthma. N Engl J Med 2006; 354(11):1117-29. DOI:10.1056/nejmoa053614
89. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol 2007; 119(2):405-13. DOI:10.1016/j.jaci.2006.11.639
90. Gern JE, Busse WW . The role of viral infections in the natural history of asthma . J. Allergy Clin. Immunol. 2000;106(2):201-12. DOI:10.1067/mai.2000.108604
91. Sigurs N , Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13 . Am. J. Respir. Crit. Care Med. 2005;171(2):137-41. DOI:10.1164/rccm.200406-730oc
92. Hamelin ME, Prince GA, Gomez AM, Kinkead R, Boivin G. Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice . J. Infect. Dis. 2006; 193(12):1634-42. DOI:10.1086/504262
93. Yoshimoto T, Min B, Sugimoto T, Hayashi N, Shikawa Y, Sasaki Y, et al. Nonredundant roles for CD1d-restricted natural killer T cells and conventional CD4+ T cells in the induction of immunoglobulin E antibodies in response to interleukin 18 treatment of mice. J Exp Med. 2003; 197(8):997-1005. DOI:10.1084/jem.20021701
94. Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu. Rev. Immunol. 1997; 15:535–562. DOI:10.1146/annurev.immunol.15.1.535
95. Takeda K, Seki S, Ogasawara K, Anzai R, Hashimoto W, Sugiura K, et al. Cytotoxic NK1.1 Ag+ alpha beta T cells with intermediate TCR induced in the liver of mice by IL-12. J. Immunol 1995; 154(9):4333-40.
96. Hachem P , Lisbonne M, Michel M, Diem S, Roongapinun S, Lefort J, et al. Alpha-galactosylceramide-induced iNKT cells suppress experimental allergic asthma in sensitized mice: role of IFNgamma . Eur. J. Immunol. 2005;35(10):2793-802. DOI:10.1002/eji.200535268
97. Matsuda H, Suda T, Sato J, Nagata T, Koide Y, Chida K, et al. α-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation . Am. J. Respir. Cell Mol. Biol. 2005;33(1):22-31. DOI:10.1165/rcmb.2004-0010oc
98. Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Sato H, E Kondo, et al. Natural killer-like nonspecifi c tumor cell lysis mediated by specifi c ligand-activated Valpha14 NKT cells . Proc. Natl. Acad. Sci. USA 1998;95(10):5690-3. DOI:10.1073/pnas.95.10.5690
99. Nagaraj S, Ziske C, Strehl J, Messmer D, Sauerbruch T, Schmidt-Wolf I G. Dendritic cells pulsed with alpha-galactosylceramide induce anti-tumor immunity against pancreatic cancer in vivo . Int. Immunol. 2006; 18(8):1279-83. DOI:10.1093/intimm/dxl059
100. Fujii S, Shimizu K, Kronenberg M, Steinman RM. Prolonged IFN-gamma-producing NKT response induced with α-galactosylceramide-loaded DCs . Nat. Immunol. 2002;3(9):867-74. DOI:10.1038/ni827
101. Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M, et al. A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer . Clin. Cancer Res. 2005; 11(5):1910-7. DOI:10.1158/1078-0432.ccr-04-1453
102. Uchida T, Horiguchi S, Tanaka Y, Yamamoto H, Kunii N, Motohashi S, et al. Phase I study of alpha-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer . Cancer Immunol. Immunother. 2008; 57(3):337-45. DOI:10.1007/s00262-007-0373-5
103. Fujii SI, Shimizu K, Hemmi H, Fukui M, Bonito AJ, Chen G, et al. Glycolipid alpha-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice . Proc. Natl. Acad. Sci. USA 2006; 103(30):11252-7. DOI:10.1073/pnas.0604812103
104. Oki S, Chiba A, Yamamura T, Miyake S . The clinical implication and molecular mechanism of preferential IL-4 production by modifi ed glycolipid-stimulated NKT cells. J. Clin. Invest. 2004; 113(11):1631-40. DOI:10.1172/jci20862
105. Bryan SA, O’Connor BJ, Matti S, Leckie MJ, Kanabar V, Khan J, et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356(9248):2149-53. DOI:10.1016/s0140-6736(00)03497-8
106. Morishima Y, Ishii Y, Kimura T, Shibuya A, Shibuya K, Hegab A, et al. Suppression of eosinophilic airway inflammation by treatment with a-galactosylceramide. Eur J Immunol. 2005; 35(10):2803-14. DOI:10.1002/eji.200525994
107. Oki S, Miyake S. Invariant Natural Killer T (iNKT) Cells in Asthma: A Novel Insight into the Pathogenesis of Asthma and the Therapeutic Implication of Glycolipid Ligands for Allergic Diseases. Allergol Int. 2007; 56(1):7-14. DOI:10.2332/allergolint.r-06-137
108. Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu. Rev. Immunol. 2005;23:877-900. DOI:10.1146/annurev.immunol.23.021704.115742
109. Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13- producing NK-T cells. Immunity 2002;17(5):629-38. DOI:10.1016/s1074-7613(02)00453-3
110. Saubermann LJ, Beck P, Jong YP, Pitman RS, Ryan MS, Kim HS, et al. Activation of natural killer T cells by alphagalactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology 2000; 119(1):119-28. DOI:10.1053/gast.2000.9114
111. Godó M, Sessler T, Hamar P. Role of Invariant Natural Killer T (iNKT) Cells in Systemic Lupus Erythematosus. Curr Med Chem. 2008; 15(18):1778-87. DOI:10.2174/092986708785132988
112. Kojo S, Adachi Y, Keino H, Tanaguchi M, Sumida T. Dysfunction of T cell receptor AV24AJ18+, BV11+ double-negative regulatory natural killer T cells in autoimmune diseases. Arthritis Rheum 2001; 44(5):1127-38. DOI:10.1002/1529-0131(200105)44:5<1127::AID-ANR194>3.0.CO;2-W.
113. Van der Vliet HJ, Blomberg BM, Nishi N, Reijm M, Voskuyl AE, Bodegraven AA et al. Circulating V(α24+) Vβ11+ NKT cell numbers are decreased in a wide variety of diseases that are characterized by auto reactive tissue damage. Clin. Immunol., 2001;100(2):144-8. DOI:10.1006/clim.2001.5060
114. Mitsuo A, Morimoto S, Nakiri Y, Suzuki J, Kaneko H, Tokano Y, et al. Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from rheumatic diseases. Rheumatology (Oxford). 2006; 45(12):1477-84.DOI:10.1093/rheumatology/kel119.



How to Cite

Kandari, S., ., R., & Chandola, A. (2023). Involvement of iNKT Cells In Bronchial Asthma. Asian Journal of Pharmaceutical Research and Development, 11(3), 67–75.