Tbx21, also known as T-Box Transcription Factor 21, is a crucial regulator of the immune response, especially the type 1 immune response. It plays a vital role in coordinating multiple aspects of the immune system, which has overall biological importance in maintaining immune homeostasis and responding to various pathogens and diseases [1,2,3,4].

In colorectal cancer (CRC), TBX21 expression is decreased compared to normal tissue and is negatively correlated with TNM stages. Ectopic expression of TBX21 inhibits cell proliferation, promotes apoptosis, and suppresses metastasis in CRC both in vitro and in vivo, through pathways such as ARHGAP29/RSK/GSK3β and MYCT1/ZO-1 [1,6]. In microsatellite stable CRC, the pathogen Fusobacterium nucleatum can induce Tbx21 promoter H3K27 acetylation and expression in CD8+ T cells, which transcriptionally represses PD-1, alleviating CD8+ T cell exhaustion and promoting effector function, thus facilitating anti-PD-1 therapy [2]. In CMS1 subtype CRC, high TBX21 expression and low methylation are associated with a survival advantage, and it may be regulated by the TP53/P53 pathway [3]. In late-onset Alzheimer's disease, TBX21 mRNA expression is elevated in the leukocytes of peripheral blood, and the TT genotype of rs41515744 plays a protective role [4]. In Asian seabass, tbx21 is associated with resistance against viral nervous necrosis (VNN), with a SNP in its first intron significantly associated with VNN resistance, and overexpression reduces NNV replication [5].

In conclusion, Tbx21 is essential for the type 1 immune response and has significant implications in multiple disease areas. Studies, especially those related to its role in CRC, microsatellite stable CRC, CMS1 subtype CRC, late-onset Alzheimer's disease, and VNN in Asian seabass, have provided insights into its functions in disease development and treatment. These findings highlight the importance of Tbx21 in understanding disease mechanisms and developing potential therapeutic strategies.