Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation

被引:67
|
作者
van Gisbergen, Klaas P. J. M. [1 ,2 ,4 ]
Kragten, Natasja A. M. [1 ,2 ,4 ]
Hertoghs, Kirsten M. L. [2 ]
Wensveen, Felix M. [3 ]
Jonjic, Stipan [3 ]
Hamann, Joerg [2 ]
Nolte, Martijn A. [1 ,2 ,4 ]
van Lier, Rene A. W. [1 ,2 ,4 ]
机构
[1] Landsteiner Lab, Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Rijeka, Dept Histol & Embryol, Rijeka, Croatia
[4] Sanquin Res CLB, Dept Hematopoiesis, Amsterdam, Netherlands
关键词
NK1(+) T-CELLS; NATURAL-KILLER; MICROBIAL INFECTION; CYTOKINE PRODUCTION; GENE-EXPRESSION; CUTTING EDGE; ACTIVATION; INTERFERON; MATURATION; LINEAGE;
D O I
10.1038/ni.2393
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The transcriptional repressor Blimp-1 mediates the terminal differentiation of many cell types, including T cells. Here we identified Hobit (Znf683) as a previously unrecognized homolog of Blimp-1 that was specifically expressed in mouse natural killer T cells (NKT cells). Through studies of Hobit-deficient mice, we found that Hobit was essential for the formation of mature thymic NKT cells. In the periphery, Hobit repressed the accumulation of interferon-gamma (IFN-gamma)-producing NK1.1(lo) NKT cells at steady state. After antigenic stimulation, Hobit repressed IFN-gamma expression, whereas after innate stimulation, Hobit induced granzyme B expression. Thus, reminiscent of the function of Blimp-1 in other lymphocytes, Hobit controlled the maintenance of quiescent, fully differentiated NKT cells and regulated their immediate effector functions.
引用
收藏
页码:864 / 871
页数:8
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