Aif1, also known as allograft inflammatory factor 1, is a calcium-binding protein. It is a key intracellular signaling molecule linked to macrophage activation, participating in processes like phagocytosis, membrane ruffling and F-actin polymerization [1]. It has cell-type specific functions and is involved in multiple pathways related to various diseases [1].

Aif1 has been associated with numerous diseases. In liver cancer, a distinct subset of AIF1 + CSF1R + MSCs induced by TNF-α promotes the generation of an inflammatory microenvironment and hepatocarcinogenesis [2]. In primary sclerosing cholangitis, proteome-wide Mendelian randomization has highlighted AIF1 as a direct target, with its genetically predicted plasma levels positively associated with an increased risk of the disease [3]. In classical swine fever virus (CSFV) Shimen infection, AIF1 in porcine alveolar macrophages is up-regulated, and it promotes CSFV replication and IL6 production [4]. In breast cancer, two AIF1 isoforms, AIF1v1 and AIF1v3, play a role in the crosstalk between the cancer and infiltrating immune cells, mediating tumor progression [5]. In spondyloarthritis/HLA-B27-associated anterior uveitis, circulating levels of AIF1 are significantly associated with a reduced risk of the disease, and AIF1 expression is lower in the HLA-B27-positive group, with myeloid cell differentiation into DCs and decreased AIF1 levels being crucial in the pathogenesis [6].

In conclusion, Aif1 is essential in macrophage-related functions and inflammation-associated processes. Its role in diseases such as liver cancer, primary sclerosing cholangitis, CSFV infection, breast cancer, and spondyloarthritis/HLA-B27-associated anterior uveitis has been revealed through various studies. Understanding Aif1 can provide insights into disease mechanisms and potentially lead to new treatment strategies for these diseases.

References:

1. De Leon-Oliva, Diego, Garcia-Montero, Cielo, Fraile-Martinez, Oscar, Alvarez-Mon, Melchor, Ortega, Miguel A. 2023. AIF1: Function and Connection with Inflammatory Diseases. In Biology, 12, . doi:10.3390/biology12050694. https://pubmed.ncbi.nlm.nih.gov/37237507/

2. Zong, Chen, Meng, Yan, Ye, Fei, Han, Zhipeng, Wei, Lixin. 2022. AIF1 + CSF1R + MSCs, induced by TNF-α, act to generate an inflammatory microenvironment and promote hepatocarcinogenesis. In Hepatology (Baltimore, Md.), 78, 434-451. doi:10.1002/hep.32738. https://pubmed.ncbi.nlm.nih.gov/35989499/

3. Chen, Lanlan, Zhao, Yuexuan, Li, Mingyue, Lv, Guoyue. 2023. Proteome-wide Mendelian randomization highlights AIF1 and HLA-DQA2 as targets for primary sclerosing cholangitis. In Hepatology international, 18, 517-528. doi:10.1007/s12072-023-10608-8. https://pubmed.ncbi.nlm.nih.gov/37950809/

4. Gong, Xiaocheng, Li, Xuepeng, You, Xin, Zhang, Xianghan, Ning, Pengbo. 2020. AIF1 was identified as an up-regulated gene contributing to CSFV Shimen infection in porcine alveolar macrophage 3D4/21 cells. In PeerJ, 8, e8543. doi:10.7717/peerj.8543. https://pubmed.ncbi.nlm.nih.gov/32110485/

5. Slim, Ferial Amira, Ouellette, Geneviève, Ennour-Idrissi, Kaoutar, Diorio, Caroline, Durocher, Francine. 2018. An isoform of AIF1 involved in breast cancer. In Cancer cell international, 18, 167. doi:10.1186/s12935-018-0663-3. https://pubmed.ncbi.nlm.nih.gov/30386176/

6. Chen, Shuming, Huang, Weidi, Wan, Qiaoqian, Li, Zhuo, Liu, Xiao. 2024. Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics. In Journal of translational medicine, 22, 271. doi:10.1186/s12967-024-05077-y. https://pubmed.ncbi.nlm.nih.gov/38475831/