The Tec Kinases Itk and Rlk Regulate NKT Cell Maturation, Cytokine Production, and Survival

1. The Tec Kinases Itk and Rlk Regulate NKT Cell Maturation,Cytokine Production, and Survival 2010. 10. 11 Jeong Hae Seong

2. NKT cell

3. NKT cell

4. NKT cell • expression of a mature TCR that binds to CD1d tetramer • stage 1 : they have low expression of CD44 and NK1.1 • stage 2 : they acquire high expression of CD44 • stage 3 : they acquire expression of NK1.1 as well as several other NK markers

5. NKT cell

6. NKT cell

7. NKT cell

8. Itk & Rlk

9. Results Fig 1.

10. Results Fig 2.

11. Results Fig 3.

12. Results Fig 4.

13. Results Fig 5.

14. Results Fig 6.

15. Discussion • Itk has the predominant role in TCR-dependent thymic selection events • Tec appears to have no important role during T cell development or in the primary activation of naive T cells • determine whether Rlk could compensate for Itk in NKT cell development, and also whether the Tec kinases Itk and Rlk are required for other aspects of NKT cell biology • NKT cells in Itk/ and Itk/Rlk/ mice shares strong similarities with defects observed in the absence of the cytokine IL-15, and more strikingly, in the absence of the T-box transcription factor, T-bet

16. Discussion • SAP- and Fyn-deficient mice reduced NKT cell numbers observed in the Tec kinase-deficient mice. • T-bet together with IL-15 is essential for terminal maturation, development of effector function, and long-term survival of NKT cells. • T-bet is regulation of IFN- transcription

17. Discussion Fig 7.

18. Discussion • AP-1 activation plays a crucial role in the terminal maturation of NKT cells. • Tec family kinases may be required for optimal TCR signaling, and defects in this pathway may lead to alterations in lineage development in the thymus.

19. Thank you