The Role Of NIK In T Cells And TRIM69 In Spermatogenesis Was Studied Using Conditioned Knockout Mice

NF-κB inducing kinase (NIK) is a central component of the noncanonical NF-κB signaling pathway. Although NIK has been extensively studied for its function in the regulation of lymphoid organ development and B-cell maturation, the role of NIK in regulating T cell functions remains unclear and controversial. Using T cell-conditional NIK knockout mice, we here demonstrate that although NIK is dispensable for thymocyte development, it has a cell-intrinsic role in regulating the homeostasis and function of peripheral T cells. T cell-specific NIK ablation reduced the frequency of effector/memory-like T cells and impaired T cell responses to bacterial infection. The T cell-conditional NIK knockout mice were also defective in generation of inflammatory T cells and refractory to the induction of a T cell-dependent autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest a crucial role for NIK in mediating the generation of effector T cells and their recall responses to antigens. Together, these findings establish NIK as a cell-intrinsic mediator of T cell functions in both immune and autoimmune responses.Ubiquitin-mediated protein degradation and modification are confirmed to play crucial roles in mammalian spermatogenesis. The TRIM family represents one of the largest subfamily of RING-finger E3 ubiquitin ligases and regulates a variety of biological processes. Trim69 is a RING domain-E3 ubiquitin ligase and specifically expressed in testis, the mRNA were enriched in postnatal third week in mice testis, suggesting that Trim69 may play a role in meiosis or spermiogenesis stage of spermatogenesis. To investigate the role of Trim69 in mammalian spermatogenesis we generated Trim69-conditional knockout mice using homologous recombination. Surprisingly, specific ablation of the RING-finger domain of Trim69 in male germ cells using Vasa-cre transgene did not affect spermatogenesis and fertility in adult males. No significant changes in germ cell apoptosis between control mice and Trim69-CKO mice. In order to identify the potential of Trim69-regulated genes we compared the genome-wide expression profiles of control mice and Trim69-CKO mice testes by mRNA sequencing. We propose that deletion of RING-finger domain of Trim69 did not infulence of spermatogenesis and germ cell survival, and its function may be related to tumor progression and immune responses.