C1QTNF4, also known as C1q/TNF-related protein 4, is a member of the C1QTNF family. It has a unique structure with two C1q domains and is involved in regulating inflammatory pathways with pro-inflammatory functions [1,2]. It may also play roles in innate immunity modulation, though its exact function in immunity and inflammation was previously poorly defined [2].

Genetic studies have linked C1QTNF4 to several diseases. In Iranian patients, the p.His198Gln mutation in C1QTNF4 is significantly associated with an increased risk of early-onset systemic lupus erythematosus (SLE) [1]. In addition, in vivo studies using C1QTNF4-transgenic, C1QTNF4-/-and AAV9-mediated VSMC-specific C1QTNF4 restoration in mouse and rat disease models showed that C1QTNF4 inhibits vascular smooth muscle cell (VSMC) proliferation and migration, and decreases intimal hyperplasia during vascular remodelling by downregulating the FAK/PI3K/AKT pathway [3].

In conclusion, C1QTNF4 is important in regulating inflammatory pathways and innate immunity. Studies using gene knockout and restoration models in mice and rats have revealed its roles in SLE and vascular remodelling. These findings provide insights into the potential mechanisms of these diseases and may offer new directions for treatment strategies related to SLE and vascular stenosis diseases [1,3].

References:

1. Pakzad, Bahram, Shirpour, Reza, Mousavi, Maryam, Akbari, Mojtaba, Salehi, Rasoul. 2020. C1QTNF4 gene p.His198Gln mutation is correlated with early-onset systemic lupus erythematosus in Iranian patients. In International journal of rheumatic diseases, 23, 1594-1598. doi:10.1111/1756-185X.13981. https://pubmed.ncbi.nlm.nih.gov/33009720/

2. Vester, Susan K, Beavil, Rebecca L, Lynham, Steven, McDonnell, James M, Vyse, Timothy J. 2021. Nucleolin acts as the receptor for C1QTNF4 and supports C1QTNF4-mediated innate immunity modulation. In The Journal of biological chemistry, 296, 100513. doi:10.1016/j.jbc.2021.100513. https://pubmed.ncbi.nlm.nih.gov/33676896/

3. Liu, Jingying, Long, Xingbo, Li, Hexin, Qin, Ziyu, Zhang, Hong. . C1q/TNF-related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling. In Clinical and translational medicine, 13, e1261. doi:10.1002/ctm2.1261. https://pubmed.ncbi.nlm.nih.gov/37221646/