Ms4a7, encoding a membrane-spanning 4-domains protein, is involved in multiple biological processes. It has been implicated in immune-related pathways and is potentially important in various disease conditions, with gene knockout models being valuable for studying its functions [1,2,3,4,5,6,7,8,9,10].

In metabolic dysfunction-associated steatohepatitis (MASH), hepatic Ms4a7 expression is strongly induced in mouse and human cases. Whole-body and myeloid-specific ablation of Ms4a7 alleviated diet-induced MASH pathologies in male mice. It was found that lipid droplets released from injured steatotic hepatocytes triggered NAM induction and MASH-associated liver injury in an Ms4a7-dependent manner, and Ms4a7 drove NLRP3 inflammasome activation via direct physical interaction [1]. In glioblastoma, the short isoform of MS4A7 (MS4A7-s) promotes activation of glioma-associated macrophages' PI3K/AKT/GSK3β pathway, leading to M2 polarization and driving malignant progression of GBM [2].

In conclusion, Ms4a7 plays a role in the pathogenesis of diseases like MASH and glioblastoma. The use of Ms4a7 knockout mouse models has revealed its significance in these disease areas, mainly through its impact on immune-related processes and cell-signaling pathways, highlighting its potential as a therapeutic target in relevant diseases.

References:

1. Zhou, Linkang, Qiu, Xiaoxue, Meng, Ziyi, Li, Siming, Lin, Jiandie D. 2024. Hepatic danger signaling triggers TREM2+ macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation. In Science translational medicine, 16, eadk1866. doi:10.1126/scitranslmed.adk1866. https://pubmed.ncbi.nlm.nih.gov/38478630/

2. Ni, Bowen, Huang, Guanglong, Yang, Runwei, Shen, Jie, Liu, Yawei. 2023. The short isoform of MS4A7 is a novel player in glioblastoma microenvironment, M2 macrophage polarization, and tumor progression. In Journal of neuroinflammation, 20, 80. doi:10.1186/s12974-023-02766-1. https://pubmed.ncbi.nlm.nih.gov/36944954/

3. Pang, Jianyu, Yu, Qian, Chen, Yongzhi, Sheng, Miaomiao, Tang, Wenru. 2022. Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer. In Journal of translational medicine, 20, 531. doi:10.1186/s12967-022-03723-x. https://pubmed.ncbi.nlm.nih.gov/36401283/

4. Zhou, Linkang, Lu, You, Qiu, Xiaoxue, Li, Siming, Lin, Jiandie D. 2025. Lipid droplet efferocytosis attenuates proinflammatory signaling in macrophages via TREM2- and MS4A7-dependent mechanisms. In Cell reports, 44, 115310. doi:10.1016/j.celrep.2025.115310. https://pubmed.ncbi.nlm.nih.gov/39954254/

5. Feng, Cheng, Shan, Mengjie, Xia, Yijun, Wang, Youbin, Huang, Yongsheng. 2022. Single-cell RNA sequencing reveals distinct immunology profiles in human keloid. In Frontiers in immunology, 13, 940645. doi:10.3389/fimmu.2022.940645. https://pubmed.ncbi.nlm.nih.gov/35990663/

6. Wu, Haoming, Feng, Jikun, Zhong, Wenjing, Wang, Xi, Yi, Jiarong. 2023. Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC. In Frontiers in immunology, 14, 1151800. doi:10.3389/fimmu.2023.1151800. https://pubmed.ncbi.nlm.nih.gov/36999020/

7. Shamseldin, Hanan E, Kurdi, Wesam, Almusafri, Fatima, Faqeih, Eissa, Alkuraya, Fowzan S. 2017. Molecular autopsy in maternal-fetal medicine. In Genetics in medicine : official journal of the American College of Medical Genetics, 20, 420-427. doi:10.1038/gim.2017.111. https://pubmed.ncbi.nlm.nih.gov/28749478/

8. Sun, Lei, Zhang, Yanli, Zhang, Chao. 2018. Distinct Expression and Prognostic Value of MS4A in Gastric Cancer. In Open medicine (Warsaw, Poland), 13, 178-188. doi:10.1515/med-2018-0028. https://pubmed.ncbi.nlm.nih.gov/29756054/

9. Houlahan, Kathleen E, Prokopec, Stephenie D, Sun, Ren X, Pohjanvirta, Raimo, Boutros, Paul C. 2015. Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin. In Toxicology and applied pharmacology, 288, 223-31. doi:10.1016/j.taap.2015.07.018. https://pubmed.ncbi.nlm.nih.gov/26232522/

10. Yang, S M, Wu, S B, Wu, J M, Sun, W P, Xiao, L Z. . [The molecular mechanism of oxaliplatin-induced peripheral neuropathic pain]. In Zhonghua yi xue za zhi, 101, 3581-3587. doi:10.3760/cma.j.cn112137-20210513-01127. https://pubmed.ncbi.nlm.nih.gov/34808752/