Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish.

Ikzf1 is a Krüppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Although the function of Ikzf1 has been studied extensively, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here we report that the genetic ablation of ikzf1 in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis. This was ascribed to impaired thymic migration, proliferation, and differentiation of hematopoietic stem/progenitor cells (HSPCs). Ccr9a and Irf4a, two indispensable factors in T lymphopoiesis, were the direct targets of Ikzf1 and were absent in the ikzf1 mutants. Genetic deletion of either ccr9a or irf4a in the corresponding mutant embryos led to obvious T cell development deficiency, which was mainly caused by disrupted thymic migration of HSPCs. Restoration of ccr9a in ikzf1 mutants obviously promoted HSPC thymus homing. However, the HSPCs then failed to differentiate into T cells. Additional replenishment of irf4a efficiently induced HSPC proliferation and T cell differentiation. Our findings further demonstrate that Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 and provide new insight into the genetic network of T lymphocyte development. © 2019 Huang et al.

Citation

Youkui Huang, Yafang Lu, Yuepeng He, Zhi Feng, Yandong Zhan, Xue Huang, Qin Liu, Jingjing Zhang, Hongtao Li, Honghui Huang, Ming Ma, Lingfei Luo, Li Li. Ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4 in zebrafish. The Journal of biological chemistry. 2019 Nov 01;294(44):16152-16163

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PMID: 31511326

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