In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 46 ( 2009-11-17), p. 19461-19466
Abstract:
Natural killer T cells expressing an invariant T-cell receptor ( i NKT) regulate activation of both innate and adaptive immunity in many contexts. i NKT cells accumulate in the liver and rapidly produce prodigious amounts of numerous cytokines upon activation, impacting the immune response to viral infection, immunosurveillance for malignant cells, and liver regeneration. However, little is known about the factors controlling i NKT homeostasis, survival and hepatic localization. Here, we report that the absence of the transcriptional regulator Id2 resulted in a severe, intrinsic defect in the accumulation of hepatic i NKT cells. Id2-deficient i NKT cells showed increased cell death in the liver, although migration and functional activity were not impaired in comparison to Id2-expressing i NKT cells. Id2-deficient i NKT cells exhibited diminished expression of CXCR6, a critical determinant of i NKT cell accumulation in the liver, and of the anti-apoptotic molecules bcl-2 and bcl-X L , compared to Id2-sufficient i NKT cells. Furthermore, survival and accumulation of i NKT cells lacking Id2 expression was rescued by deficiency in bim, a key pro-apoptotic molecule. Thus, Id2 was necessary to establish a hepatic i NKT cell population, defining a role for Id2 and implicating the Id targets, E protein transcription factors, in the regulation of i NKT cell homeostasis.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0908249106
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2009
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Permalink