Rorc, also known as retinoic acid receptor-related orphan receptor gamma, is a key DNA-binding transcription factor. It is responsible for the differentiation of T helper 17 (Th17) cells, playing important roles in lymphoid organogenesis, thymopoiesis, and lymph node organogenesis. It is also involved in the development of the lymphatic system and is associated with pathways related to inflammation, autoimmune diseases, and cancer [3].

In Rorc knockout mouse models, it was found that Rorc-expressing cells negatively regulate tertiary lymphoid structure (TLS) formation. In the absence of these cells, TLSs not only increase in number but also acquire anti-tumorigenic properties in the context of inflammation-associated liver cancer [2]. Additionally, Rorc is necessary for optimal Th17 responses in peripheral tissues. Although dispensable for Th17 cell differentiation, its absence in T cells led to reductions in RORγt expression and effector function among Th17 cells [1].

In conclusion, Rorc is essential for Th17 cell-related functions and lymphoid organ development. Gene knockout mouse models have revealed its role in regulating the immune microenvironment in cancer and maintaining Th17 cell effector programs. These findings suggest its potential as a biomarker and therapeutic target in diseases related to abnormal Th17 cell function and lymphatic system disorders.

References:

1. Hall, Jason A, Pokrovskii, Maria, Kroehling, Lina, Lee, June-Yong, Littman, Dan R. 2022. Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element. In Immunity, 55, 2027-2043.e9. doi:10.1016/j.immuni.2022.09.013. https://pubmed.ncbi.nlm.nih.gov/36243007/

2. Cinnamon, Einat, Stein, Ilan, Zino, Elvira, Parnas, Oren, Pikarsky, Eli. 2024. RORc-expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions. In Journal of hepatology, , . doi:10.1016/j.jhep.2024.12.015. https://pubmed.ncbi.nlm.nih.gov/39710149/

3. Michelini, Sandro, Ricci, Maurizio, Serrani, Roberta, Dundar, Munis, Bertelli, Matteo. 2020. Possible Role of the RORC Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants. In Lymphatic research and biology, 19, 129-133. doi:10.1089/lrb.2020.0030. https://pubmed.ncbi.nlm.nih.gov/32960152/