Defb4, also known as human beta-defensin 2 (hBD-2), encodes an antimicrobial peptide that plays a crucial role in the innate immune response at epithelial surfaces. It is involved in the NF-κB signaling pathway, as its expression can be regulated by NF-κB binding to its promoter region [5]. Defb4 is inducible in response to proinflammatory signals like cytokines and bacterial molecules, and thus is important for the body's defense against pathogens [5].

In a mouse model, deletion of the antimicrobial peptide gene Defb4 impairs the virulence by Rv2780 during Mycobacterium tuberculosis infection, suggesting that Defb4 is necessary for an effective immune response against this pathogen [3]. In human studies, a lower DEFB4 copy number was associated with dermatophytosis, along with elevated serum hBD-2 and IL-22 levels, indicating a gene/cytokine interaction in this infection [1]. Higher DEFB4 copy numbers were associated with SLE, ANCA-associated small vasculitis, and Crohn's disease, suggesting its involvement in these autoimmune and inflammatory conditions [2,4].

In conclusion, Defb4 is essential for the innate immune response, especially in defending against pathogens like Mycobacterium tuberculosis. Studies, including those using gene-deletion models in mice, have revealed its significance in various disease areas such as infectious and autoimmune diseases. Understanding Defb4's role can potentially lead to new strategies for treating these conditions.

References:

1. Jaradat, Sameh W, Cubillos, Susana, Krieg, Nadine, Hipler, Uta-Christina, Norgauer, Johannes. 2014. Low DEFB4 copy number and high systemic hBD-2 and IL-22 levels are associated with dermatophytosis. In The Journal of investigative dermatology, 135, 750-758. doi:10.1038/jid.2014.369. https://pubmed.ncbi.nlm.nih.gov/25178103/

2. Zhou, Xu-Jie, Cheng, Fa-Juan, Lv, Ji-Cheng, Zhao, Ming-Hui, Zhang, Hong. 2012. Higher DEFB4 genomic copy number in SLE and ANCA-associated small vasculitis. In Rheumatology (Oxford, England), 51, 992-5. doi:10.1093/rheumatology/ker419. https://pubmed.ncbi.nlm.nih.gov/22302058/

3. Peng, Cheng, Cheng, Yuanna, Ma, Mingtong, Ge, Baoxue, Wang, Lin. 2024. Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine. In Nature communications, 15, 4216. doi:10.1038/s41467-024-48588-4. https://pubmed.ncbi.nlm.nih.gov/38760394/

4. Bentley, Robert W, Pearson, John, Gearry, Richard B, Merriman, Tony R, Roberts, Rebecca L. 2009. Association of higher DEFB4 genomic copy number with Crohn's disease. In The American journal of gastroenterology, 105, 354-9. doi:10.1038/ajg.2009.582. https://pubmed.ncbi.nlm.nih.gov/19809410/

5. Woo, Jeong-Im, Kil, Sung-Hee, Pan, Huiqi, Lim, David J, Moon, Sung K. 2013. Distal NF-kB binding motif functions as an enhancer for nontypeable H. influenzae-induced DEFB4 regulation in epithelial cells. In Biochemical and biophysical research communications, 443, 1035-40. doi:10.1016/j.bbrc.2013.12.091. https://pubmed.ncbi.nlm.nih.gov/24368180/