The transcription factor Th-POK negatively regulates Th17 differentiation in V?14i NKT cells.

ABSTRACT: The majority of mouse V?14 invariant natural killer T (V?14i NKT) cells produce several cytokines, including IFN? and IL-4, very rapidly after activation. A subset of these cells, known as NKT17 cells, however, differentiates in the thymus to preferentially produce IL-17. Here, we show that the transcription factor-known as T helper, Poxviruses, and Zinc-finger and Krüppel family, (Th-POK)-represses the formation of NKT17 cells. V?14i NKT cells from Th-POK-mutant helper deficient (hd/hd) mice have increased transcripts of genes normally expressed by Th17 and NKT17 cells, and even heterozygosity for this mutation leads to dramatically increased numbers of V?14i NKT cells that are poised to express IL-17, especially in the thymus and lymph nodes. In addition, using gene reporter mice, we demonstrate that NKT17 cells from wild-type mice express lower amounts of Th-POK than the majority population of V?14i NKT cells. We also show that retroviral transduction of Th-POK represses the expression of the Th17 master regulator ROR?T in V?14i NKT-cell lines. Our data suggest that NKT17-cell differentiation is intrinsically regulated by Th-POK activity, with only low levels of Th-POK permissive for the differentiation of NKT17 cells.

SUBMITTER: Engel I 

PROVIDER: S-EPMC3512232 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature