Rorc, also known as retinoic acid receptor-related orphan receptor C, is a DNA-binding transcription factor. It is the key transcription factor responsible for the differentiation of T helper 17 (Th17) cells, playing roles in lymphoid organogenesis, thymopoiesis, and lymph node organogenesis. Rorc-expressing immune cells are involved in inflammation, autoimmune disease, and cancer, and the gene is associated with multiple biological pathways and disease conditions [1,2]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In Rorc knockout mouse models, Rorc-expressing cells were found to negatively regulate tertiary lymphoid structure (TLS) formation in the context of inflammation-associated liver cancer. In their absence, excess TLSs formed and became anti-tumorigenic, reducing tumor load [2]. Additionally, Notch signaling promotes the upregulation of RORC, enabling the acquisition of effector functions in multi-potent and uni-potent innate lymphoid cell precursors, and interfering with RORC compromises innate lymphoid cell 3 (ILC3) effector functions and generally suppresses ILC production from multi-potent precursors [3].

In conclusion, Rorc is essential for Th17 cell differentiation and has important functions in lymphoid organogenesis. Through model-based research, especially knockout mouse models, it has been revealed that Rorc plays a role in regulating TLS formation in liver cancer and is involved in the differentiation of innate lymphoid cells. These findings contribute to our understanding of its role in immune-related diseases and cancer.