Scgb1a1, also known as club cell secretory protein (CCSP), is one of the most abundant proteins in the lung, primarily produced by club cells of the distal airway epithelium. It has anti-inflammatory effects, dampening acute and chronic lung inflammation, and is thus a potential therapeutic modality in lung disease [1].

In murine models, Scgb1a1-deficient mice showed down-regulation of biological pathways related to antigen presentation, anti-viral immunity and inflammation in alveolar macrophages (AMs) compared to Scgb1a1-sufficient counterparts. AMs from Scgb1a1-deficient mice also had an early activation of inflammatory pathways. Exogenous supplementation of SCGB1a1 protein reduced AM responses to microbial stimuli [2]. In an ovalbumin-induced mouse model of asthma, both Scgb1a1 and FoxA2 were downregulated, and Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation, confirming Scgb1a1's anti-inflammatory role in asthma [3]. In a rat COPD model, high-throughput mRNA sequencing identified upregulated Scgb1a1, and in vitro assays showed that SCGB1A1 inhibits LPS-induced macrophage activation and PHA-induced lymphocyte proliferation, suggesting its contribution to splenic immune dysfunction in COPD [4].

In conclusion, Scgb1a1 plays a crucial role in modulating inflammation and immune responses, especially in the context of lung-related diseases such as asthma and COPD. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into its role in disease-associated biological processes and potentially guiding future therapeutic strategies.

References:

1. Martinu, Tereza, Todd, Jamie L, Gelman, Andrew E, Guerra, Stefano, Palmer, Scott M. 2022. Club Cell Secretory Protein in Lung Disease: Emerging Concepts and Potential Therapeutics. In Annual review of medicine, 74, 427-441. doi:10.1146/annurev-med-042921-123443. https://pubmed.ncbi.nlm.nih.gov/36450281/

2. Xu, Min, Yang, Wei, Wang, Xuanchuan, Nayak, Deepak Kumar. 2020. Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity. In Frontiers in immunology, 11, 584310. doi:10.3389/fimmu.2020.584310. https://pubmed.ncbi.nlm.nih.gov/33117399/

3. Zhu, Lingxiang, An, Lingling, Ran, Di, Liao, Shu-Yi, Chen, Yin. . The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma. In American journal of respiratory cell and molecular biology, 60, 695-704. doi:10.1165/rcmb.2018-0199OC. https://pubmed.ncbi.nlm.nih.gov/30576223/

4. Chen, Xinye, Wang, Qiujie, Gong, Mingyan, Jiang, Shanping, Shi, Jianting. 2025. SCGB1A1 as a Key Regulator of Splenic Immune Dysfunction in COPD: Insights From a Murine Model. In International journal of chronic obstructive pulmonary disease, 20, 497-509. doi:10.2147/COPD.S506332. https://pubmed.ncbi.nlm.nih.gov/40060920/