ReI/NF-kB family member ReIA regulates NK1.1- to NK1.1+ transition as well as IL-15-induced expansion of NKT cells
Vallabhapurapu, Sivakumar, Powolny-Budnicka, Iwona, Riemann, Marc, Schmid, Roland M., Paxian, Stephan, Pfeffer, Klaus, Korner, Heinrich, and Weih, Falk (2008) ReI/NF-kB family member ReIA regulates NK1.1- to NK1.1+ transition as well as IL-15-induced expansion of NKT cells. European Journal of Immunology, 38 (12). pp. 3508-3519.
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View at Publisher Website: http://dx.doi.org/10.1002/eji.200737830
Development of NKT cells was shown to depend on lymphotoxin (LT) and IL-15 signaling pathways as well as on cytokine receptor common chain. After positive selection, NKT-cell precursors transit through progressive maturation stages including proliferative expansion within the NK1.1- window. The transcription factors that integrate different signaling pathways into different stages of NKT-cell development are not well characterized. Here, we show that the ReI/NF-B family member ReIA regulates the NK1.1- to NK1.1+ transition during NKT-cell development. ReIA is also required for both IL-15- and IL-7-induced proliferation of CD44hiNK1.1- NKT-cell precursors. Activation of the invariant NKT-cell receptor induces both IL-15 receptor and chains' expression in an NF-B-dependent manner, suggesting a molecular mechanism by which NF-B regulates NKT-cell development. NF-B also regulates TCR-induced expression of LT- and LT- within NKT cells. In contrast to previous reports, however, we show that LT signaling is dispensable for thymic NKT-cell development but is essential for their colonization of peripheral organs such as liver.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||NKT cells; Lymphotoxin; common chain; IL-15; liver; lymphotoxin • NKT cells|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%|
|Deposited On:||10 Feb 2010 11:59|
|Last Modified:||18 Oct 2013 00:47|
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