Arid5a, also known as AT-rich interactive domain 5A, is a nucleic acid-binding protein with dual functions as a transcription factor co-factor and an RNA-binding protein [1,2,4]. It contributes to cell growth, differentiation, and is involved in maintaining cellular homeostasis. Arid5a is associated with multiple pathways such as TLR4-activated NF-κB and MAPK pathways, which regulate its expression [5]. It has significance in immune regulation, inflammation, and diseases like autoimmunity, cancer, and obesity [1,2,4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In KO mouse models, Arid5a-/-mice were refractory to autoantibody-induced glomerulonephritis (AGN), with reduced myeloid infiltration and impaired expression of IL-17-dependent cytokines and transcription factors, indicating its role in driving IL-17-dependent renal autoimmunity at the level of ribosome interactions and translation [3]. Inhibition of Arid5a in mouse models prevented septic shock, experimental autoimmune encephalomyelitis, and acute lung injury, suggesting its involvement in these inflammatory conditions [2]. Deletion of Arid5a in tumor cell lines enhanced antitumor immunity in immunocompetent mice, highlighting its role in tumor immune evasion [6]. In lipopolysaccharide-induced kidney injury in mice, Arid5a knockout led to lower expression of Il-6 and Pai-1 mRNA, indicating its role in the Arid5a/IL-6/PAI-1 signaling-related kidney injury [7].

In conclusion, model-based research shows that Arid5a is crucial in immune regulation, inflammation, and tumor-related processes. KO/CKO mouse models have revealed its significance in diseases such as autoantibody-induced glomerulonephritis, septic shock, experimental autoimmune encephalomyelitis, acute lung injury, tumor immune evasion, and lipopolysaccharide-induced kidney injury, providing insights into potential therapeutic targets for these diseases.

References:

1. Nyati, Kishan Kumar, Zaman, Mohammad Mahabub-Uz, Sharma, Praveen, Kishimoto, Tadamitsu. 2020. Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity. In Trends in immunology, 41, 255-268. doi:10.1016/j.it.2020.01.004. https://pubmed.ncbi.nlm.nih.gov/32035762/

2. Nyati, Kishan Kumar, Kishimoto, Tadamitsu. 2022. Recent Advances in the Role of Arid5a in Immune Diseases and Cancer. In Frontiers in immunology, 12, 827611. doi:10.3389/fimmu.2021.827611. https://pubmed.ncbi.nlm.nih.gov/35126382/

3. Li, Yang, Vyas, Shachi P, Mehta, Isha, Das, Jishnu, Gaffen, Sarah L. 2024. The RNA binding protein Arid5a drives IL-17-dependent autoantibody-induced glomerulonephritis. In The Journal of experimental medicine, 221, . doi:10.1084/jem.20240656. https://pubmed.ncbi.nlm.nih.gov/39058386/

4. Nyati, Kishan Kumar, Kishimoto, Tadamitsu. 2022. The emerging role of Arid5a in cancer: A new target for tumors. In Genes & diseases, 10, 813-824. doi:10.1016/j.gendis.2021.12.012. https://pubmed.ncbi.nlm.nih.gov/37396543/

5. Nyati, Kishan Kumar, Agarwal, Riddhi Girdhar, Sharma, Praveen, Kishimoto, Tadamitsu. 2019. Arid5a Regulation and the Roles of Arid5a in the Inflammatory Response and Disease. In Frontiers in immunology, 10, 2790. doi:10.3389/fimmu.2019.02790. https://pubmed.ncbi.nlm.nih.gov/31867000/

6. Parajuli, Gyanu, Tekguc, Murat, Wing, James B, Kishimoto, Tadamitsu, Hashimoto, Shigeru. 2021. Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine Expression. In Cancer immunology research, 9, 862-876. doi:10.1158/2326-6066.CIR-21-0014. https://pubmed.ncbi.nlm.nih.gov/34006522/

7. Tanaka, Koki, Harada, Hiroki, Kamuro, Hiroyasu, Fujio, Yasushi, Obana, Masanori. . Arid5a/IL-6/PAI-1 Signaling Is Involved in the Pathogenesis of Lipopolysaccharide-Induced Kidney Injury. In Biological & pharmaceutical bulletin, 46, 1753-1760. doi:10.1248/bpb.b23-00482. https://pubmed.ncbi.nlm.nih.gov/38044094/