The Roles Of iNKT Cells In Asthma

พญ . รังสิมา เหรียญตระกูล IMMUNOLOGY DIVISION DEPARTMENT OF MICROBIOLOGY FACULTY OF MEDICINE CHULALONGKORN UNIVERSITY The Role of iNKT Cells in Asthma

Allergic Bronchial Asthma ,[object Object],[object Object]

[object Object],[object Object],[object Object]

NKT Cells ,[object Object],[object Object],[object Object],[object Object]

Discovery of NKT Cells ,[object Object],[object Object],V  14 J  18 Imai et al., 1986 Koseki et al., 1989 Lantz and Bendelec, 1994 Makino et al., 1995 Cui et al., 1997

[object Object],[object Object],[object Object],Budd et al., 1987 Fowlkes et al., 1987 Ballas and Rasmussen, 1990 Sykes, 1990

[object Object],[object Object],Lantz and Bendelac. J.Exp.Med. 1994 Makino et al. Int. Immunol. 1995 Taniguchi et al. Proc. Natl.Acad.Sci. 1996

“ NKT Cell” ,[object Object],[object Object],[object Object],[object Object],[object Object]

NKT Cell Role ,[object Object],[object Object],[object Object],Stetson et al. J.Exp.Med. 2003 IFN-  IL-4 Yoshimoto et al. Science.1995 Kinjo et al. Nature., 2005

Classification of NKT Cells Type I NKT Cells ,[object Object],[object Object],Type II NKT Cells ,[object Object],[object Object],Type III NKT Cells ,[object Object]

Type I NKT Cells ,[object Object],[object Object],[object Object],[object Object],[object Object],Kawano et al., 1997

Type I NKT Subsets ,[object Object],[object Object],Gumperz et al., 2002 Lee et al., 2002a

iNKT Microbial Recognition ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Terabe M et al. Adv.Canc.Res. 2008

iNKT Self-Antigen Recognition ,[object Object],[object Object],[object Object],[object Object],[object Object],Terabe M et al. Adv.Canc.Res. 2008

Asthma and NKT Cells ,[object Object],[object Object],[object Object],[object Object],Akbari et al. Nat Med 2003

[object Object],[object Object],[object Object],[object Object],Lisbonne et al. J.Immunol. 2003

iNKT Cells in the Induction of AHR ,[object Object],[object Object],[object Object],Lisbonne et al. J.Immunol.2003 Akbari et al. Nat. Med. 2003

The Importance iNKT Cells in AHR Development ,[object Object],[object Object],Matsuda et al. Am.J.Respir.Cell.Mol.Biol.2005 Hachem et al. Eur.J.Immunol.2005 Morishima et al. Eur.J.Immunol. 2005 Meyer et al. Proc.Natl.Acad.Sci. 2006

[object Object],[object Object],[object Object],Meyer et al. Annu.Rev.Med. 2008 Maeda et al. J.Immunol. 2004 Zhang et al. J.Exp. Med. 1996

iNKT Cells in Human Asthma ,[object Object],[object Object],[object Object],CD4+ Invariant T-Cell-Receptor+ Natural Killer T Cells in Bronchial Asthma Akbari O et al. NEJM. 2006

[object Object],Akbari O et al. NEJM. 2006

[object Object],[object Object],[object Object],Akbari O et al. NEJM. 2006

Corticosteroid-treated Corticosteroid-untreated Akbari O et al. NEJM. 2006

iNKT Cells in Human Asthma ,[object Object],V alpha 24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement Sen Y et al . J.Immunol. 2005

87% Sen Y et al . J.Immunol. 2005

[object Object],Sen Y et al . J.Immunol. 2005

CCR9 and V24 i NK T cell distribution Sen Y et al . J.Immunol. 2005

Asthmatic CCR9-expressing V24i NKT cells induced Th2 bias in CD3 T cells IL-4 IL-13 Sen Y et al . J.Immunol. 2005

IL-4 IL-13 Sen Y et al . J.Immunol. 2005

Confirm the function of different V24 i NKT cells IL-4 IL-13 Sen Y et al . J.Immunol. 2005

Transwell stimulations Sen Y et al . J.Immunol. 2005

CD226 expression in V24 i NKT cells Sen Y et al . J.Immunol. 2005

CCR9 and CD226 activation Sen Y et al . J.Immunol. 2005

Kay AB.NEJM. 2006 The Two Pathways

iNKT Cells in the Current Asthma Model Umetsu. Nature. 2006

iNKT Cells in Human Asthma ,[object Object],Spinozzi et al. Immmunol. Allergy Clin. North Am. 2007 Pham-Thi N et al. JACI. 2006 Pham-Thi N et al. NEJM. 2006 Hamzaoui A et al. Mediat. Inflamm. 2006 Sen Y et al. J. Immunol. 2005

[object Object],[object Object],Thomas SY et al. NEJM. 2006 Vijayanad P et al. NEJM. 2007

[object Object],[object Object],[object Object],Natural killer T Cells in the lungs of patients with asthma Umetsu et al. JACI. 2009

Adjusted percentages of iNKT cells/Tcells

Asthma Phenotypes Mild-moderate asthma Persistent severe asthma Th2 cell iNKT cell iNKT cell

Therapeutic Potentials ,[object Object],[object Object],[object Object],[object Object],Oki and Miyake. Allergol.Internat. 2007

The Roles Of iNKT Cells In Asthma

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The Roles Of iNKT Cells In Asthma