| First Author | Engel I | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 23 | Pages | 4524-32 |
| PubMed ID | 23034280 | Mgi Jnum | J:190936 |
| Mgi Id | MGI:5450776 | Doi | 10.1182/blood-2012-01-406280 |
| Citation | Engel I, et al. (2012) The transcription factor Th-POK negatively regulates Th17 differentiation in Valpha14i NKT cells. Blood 120(23):4524-32 |
| abstractText | The majority of mouse Valpha14 invariant natural killer T (Valpha14i NKT) cells produce several cytokines, including IFNgamma 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 Kruppel family, (Th-POK)-represses the formation of NKT17 cells. Valpha14i 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 Valpha14i 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 Valpha14i NKT cells. We also show that retroviral transduction of Th-POK represses the expression of the Th17 master regulator RORgammaT in Valpha14i 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. |
