Gpr35, a G protein-coupled receptor, plays a notable role in modulating inflammatory responses [1]. It has been associated with multiple biological pathways, such as the gut-microbe-brain metabolic axis and neutrophil recruitment. Gpr35 can be activated by various ligands including kynurenic acid, 5-hydroxyindoleacetic acid (5-HIAA), and others. The use of genetic models, like gene knockout (KO) mouse models, has been crucial in understanding its function [4,5].

In KO mouse models, genetic deletion of Gpr35 in the gut epithelium induces depressive-like behavior in a microbiome-dependent manner, suggesting its role in the gut-microbe-brain axis regulating depression [2]. Also, Gpr35-deficient neutrophils are less recruited from blood vessels into inflamed tissue, and the mice are less efficient in clearing peritoneal bacteria, highlighting its importance in innate immune responses [3].

In conclusion, Gpr35 is essential in regulating inflammation, gut-microbe-brain-related behaviors, and neutrophil-mediated innate immune responses. The gene knockout mouse models have significantly contributed to understanding its role in depression-related behaviors and immune-mediated bacterial clearance, providing insights into potential therapeutic targets for inflammatory diseases and mental health disorders.

References:

1. Wu, Yetian, Zhang, Pei, Fan, Hongjie, Liang, Xinmiao, Chen, Yang. 2023. GPR35 acts a dual role and therapeutic target in inflammation. In Frontiers in immunology, 14, 1254446. doi:10.3389/fimmu.2023.1254446. https://pubmed.ncbi.nlm.nih.gov/38035084/

2. Cheng, Lingsha, Wu, Haoqian, Cai, Xiaoying, Hao, Haiping, Zheng, Xiao. 2024. A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior. In Cell host & microbe, 32, 227-243.e6. doi:10.1016/j.chom.2023.12.009. https://pubmed.ncbi.nlm.nih.gov/38198925/

3. De Giovanni, Marco, Tam, Hanson, Valet, Colin, Looney, Mark R, Cyster, Jason G. 2022. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. In Cell, 185, 815-830.e19. doi:10.1016/j.cell.2022.01.010. https://pubmed.ncbi.nlm.nih.gov/35148838/

4. Kaya, Berna, Melhem, Hassan, Niess, Jan Hendrik. 2021. GPR35 in Intestinal Diseases: From Risk Gene to Function. In Frontiers in immunology, 12, 717392. doi:10.3389/fimmu.2021.717392. https://pubmed.ncbi.nlm.nih.gov/34790192/

5. Im, Dong-Soon. 2023. Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand. In Archives of pharmacal research, 46, 550-563. doi:10.1007/s12272-023-01449-y. https://pubmed.ncbi.nlm.nih.gov/37227682/