Yasuoka Toshiaki, Kuwahara Makoto, Yamada Takeshi, Maruyama Saho, Suzuki Junpei, Taniguchi Masaru, Yasukawa Masaki, Yamashita Masakatsu
Department of Obstetrics and Gynecology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, Japan.
PLoS One. 2016 Jun 10;11(6):e0157395. doi: 10.1371/journal.pone.0157395. eCollection 2016.
Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of Gfi1-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific Gfi1-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1pos iNKT cells was significantly reduced. Furthermore, CD4pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific Gfi1-deficient mice. The α-GalCer-dependent production of IFN-γand Th2 cytokines, but not IL-17A, was severely reduced in T cell-specific Gfi1-deficient mice. In addition, a reduction of the α-GalCer-induced anti-tumor activity was observed in Gfi1-deficient mice. These findings demonstrate the important role of Gfi1 in regulating the development and function of NKT1- and NKT2-type iNKT cell subsets.
Gfi1在多种造血谱系细胞的发育和维持中发挥重要作用。然而，Gfi1缺陷对iNKT细胞分化的影响仍不清楚。我们在此证明Gfi1在调节iNKT细胞亚群发育中起关键作用。在T细胞特异性Gfi1缺陷小鼠的胸腺中，iNKT细胞正常发育至2期，而3期NK1.1阳性iNKT细胞数量显著减少。此外，在T细胞特异性Gfi1缺陷小鼠的外周器官中，CD4阳性iNKT细胞选择性减少。在T细胞特异性Gfi1缺陷小鼠中，α-GalCer依赖的IFN-γ和Th2细胞因子的产生，但不包括IL-17A，严重减少。此外，在Gfi1缺陷小鼠中观察到α-GalCer诱导的抗肿瘤活性降低。这些发现证明了Gfi1在调节NKT1型和NKT2型iNKT细胞亚群的发育和功能中的重要作用。
