Il23a, also known as p19, is a subunit of the pro-inflammatory cytokine interleukin-23 (IL-23). IL-23, composed of Il23a and IL-12/23B (p40), drives the differentiation and activation of T helper 17 (Th17) cells, leading to the production of cytokines like IL-17A, IL-17F, IL-6, IL-22, and TNF-α. This cytokine is mainly produced by macrophages and dendritic cells in response to signals. The IL-23/IL-17 pathway is crucial in protective immune responses to certain infections but is also involved in chronic immune-mediated inflammation [2].

In psoriasis, single-cell analysis of human skin identified that CD14+ type 3 dendritic cells in lesional skin increased and co-produced IL1B and Il23a, which are pathological in psoriasis [1]. In the context of cognitive impairment caused by bortezomib exposure, brain endothelial-specific ablation of Il23a ameliorated microglia activation and cognitive dysfunction, suggesting that the endothelial TFEB-STAT3-Il23A axis is critical for initiating bortezomib-mediated aberrant microglial activation [3]. Additionally, in inflammatory bowel disease, higher mucosal Il23a expression was associated with a greater likelihood of achieving remission with ustekinumab treatment, indicating its potential as a biomarker for treatment response prediction [4].

In conclusion, Il23a plays a significant role in the IL-23/IL-17 pathway, which is involved in both normal immune responses and the pathogenesis of various inflammatory diseases such as psoriasis, cognitive impairment related to chemotherapy, and inflammatory bowel disease. Studies using gene-targeted mouse models, like the endothelial-specific Il23a knockout, have provided valuable insights into its role in these disease conditions, highlighting its potential as a therapeutic target or biomarker.