Liver type 1 innate lymphoid cells (ILC1s), also known as liver-resident NK cells, play a crucial role in regulating T cell responses during viral infections, but the transcriptional regulation invovled in this process has not yet been explored.
In this study, we found that the transcription factor ATF3 was significantly upregulated in liver ILC1s during LCMV Clone 13 infection. In constitutive and conditional Atf3 knockout mice, the proportion and number of liver ILC1s were significantly increased, leading to an enhanced immunosuppressive effect on antigen-specific CD8⁺ T cells. This impaired CD8⁺ T cell repsonses resulted in delayed viral clearance and mitigated liver injury. RNA-seq analysis revealed that genes related to ferrotosis were downregulated in ATF3-deficient ILC1s, suggesting a role of ATF3 in restraining the survival of ILC1s with immunosupprevise functions during viral infections. Further studies are required to explore whether ATF3 directly influences ILC1-CD8⁺ T cell crosstalk.