Scgb1a1, also known as club cell secretory protein (CCSP), is one of the most abundant proteins in the lung, mainly produced by club cells of the distal airway epithelium [1]. It plays a role in dampening acute and chronic lung inflammation [1]. In addition, it influences alveolar macrophage-mediated inflammation and immunity, and is involved in antigen presentation, anti-viral immunity and inflammation pathways [2].

In a murine model, AMs from Scgb1a1 -deficient mice showed an early activation of inflammatory pathways compared with that from Scgb1a1 -sufficient mice, and exogenous supplementation of SCGB1a1 protein significantly reduced AM responses to microbial stimuli [2]. Also, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when exposed to ovalbumin, confirming its anti -inflammatory role in protecting against asthma phenotypes [3]. In a rat COPD model, high -throughput mRNA sequencing identified SCGB1A1 as notably upregulated, and in vitro assays confirmed that SCGB1A1 inhibits LPS -induced macrophage activation and PHA -induced lymphocyte proliferation, suggesting it contributes to splenic immune dysfunction in COPD [4].

In conclusion, Scgb1a1 has essential anti -inflammatory functions in the lung, influencing alveolar macrophage -mediated responses and protecting against asthma phenotypes. Its role in COPD -related splenic immune dysfunction is also emerging. Gene knockout mouse models have been crucial in revealing these functions, providing insights into its role in specific disease areas such as asthma and COPD.