Retnlg-KO Mouse

Retnlg, encoding resistin-like molecule (RELM)-γ, seems to be involved in immune-related functions. It is associated with the regulation of immune cell-mediated responses and may play a role in inflammation-related pathways. Its biological importance lies in its potential influence on the modulation of the immune system, which is crucial for maintaining health and responding to various challenges [1,2,3,4,5,6,7,8,9]. Genetic models could potentially provide in-depth insights into its exact functions.

In the study of mesenchymal stem/stromal cell-induced myeloid-derived suppressor cells (MDSCs), Retnlg was highly expressed in these MDSCs, but it had no direct effects on T-cell proliferation, Treg expansion, or splenocyte activation [1]. In acute inflammatory lung injury, the gene was differentially expressed in mice with ALI caused by pulmonary and extrapulmonary factors, suggesting its role in the immune response heterogeneity in such conditions [2]. In skin wound healing, the expression of RETNLG was associated with migrating neutrophils, and human umbilical cord mesenchymal stem cell-derived exosomes, which affected the differentiation of macrophages and neutrophils, may have an impact on the function related to Retnlg [3]. In the context of gastric pathology, Retnlg was highly enriched in gastric CD11b+Ly6G+ granulocytic MDSCs following Helicobacter felis infection [4]. In atopic dermatitis mouse models, topical emollient treatment downregulated genes involved in leucocyte chemotaxis including Retnlg, reducing basophil infiltration and activation in the lung [5]. In Clonorchis sinensis-infected mouse livers, Retnlg was up-regulated at both gene and protein levels, being associated with liver fibrosis and inflammation [6]. In bladder cancer, a subpopulation of RETNLG+LCN2+ senescence-like neutrophils preferentially accumulated in the male tumor microenvironment, having a strong immunosuppressive effect [7]. In preeclampsia, pro-inflammatory macrophages inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ granulocyte MDSCs at the maternal-fetal interface, leading to PE-like symptoms in mice [8]. In ulcerative colitis, Retnlg was identified as a biomarker for assessing BPA-induced colitis [9].

In conclusion, Retnlg appears to be intricately involved in multiple immune-related biological processes and disease conditions, including immune cell-mediated responses, inflammation, and wound healing. Findings from various in vivo models have shed light on its role in diseases such as atopic dermatitis, bladder cancer, preeclampsia, and ulcerative colitis, highlighting its potential as a therapeutic target or biomarker in these disease areas.

References:

1. Lee, Hyun Ju, Choi, Yoo Rim, Ko, Jung Hwa, Ryu, Jin Suk, Oh, Joo Youn. 2024. Defining mesenchymal stem/stromal cell-induced myeloid-derived suppressor cells using single-cell transcriptomics. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 1970-1983. doi:10.1016/j.ymthe.2024.04.026. https://pubmed.ncbi.nlm.nih.gov/38627968/

2. Kang, Zhi-Ying, Huang, Qian-Yu, Zhen, Ning-Xin, Zhang, Zhao-Cai, Tian, Bao-Ping. 2024. Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury. In Frontiers in immunology, 15, 1382449. doi:10.3389/fimmu.2024.1382449. https://pubmed.ncbi.nlm.nih.gov/38745657/

3. Liu, Yuanyuan, Zhang, Mingwang, Liao, Yong, Zhang, Xingyue, Yang, Rongya. 2023. Human umbilical cord mesenchymal stem cell-derived exosomes promote murine skin wound healing by neutrophil and macrophage modulations revealed by single-cell RNA sequencing. In Frontiers in immunology, 14, 1142088. doi:10.3389/fimmu.2023.1142088. https://pubmed.ncbi.nlm.nih.gov/36999022/

4. Kao, Krystal D, Grasberger, Helmut, El-Zaatari, Mohamad. 2023. The Cxcr2+ subset of the S100a8+ gastric granylocytic myeloid-derived suppressor cell population (G-MDSC) regulates gastric pathology. In Frontiers in immunology, 14, 1147695. doi:10.3389/fimmu.2023.1147695. https://pubmed.ncbi.nlm.nih.gov/37744359/

5. Zhang, Jiayi, Xu, Xintian, Wang, Xiaopan, Chen, Lihong, Zheng, Jie. 2023. Topical emollient prevents the development of atopic dermatitis and atopic march in mice. In Experimental dermatology, 32, 1007-1015. doi:10.1111/exd.14806. https://pubmed.ncbi.nlm.nih.gov/37029953/

6. Zhan, Tingzheng, Wu, Yuhong, Deng, Xueling, Liu, Dengyu, Tang, Zeli. 2023. Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver. In Frontiers in cellular and infection microbiology, 13, 1286977. doi:10.3389/fcimb.2023.1286977. https://pubmed.ncbi.nlm.nih.gov/38076459/

7. Zhu, Qingchen, Zhang, Guiheng, Cao, Ming, Qin, Jun, Xiao, Yichuan. 2025. Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer. In Nature immunology, 26, 722-736. doi:10.1038/s41590-025-02126-6. https://pubmed.ncbi.nlm.nih.gov/40217111/

8. Fei, Haiyi, Lu, Xiaowen, Shi, Zhan, Zhang, Songying, Jiang, Lingling. 2025. Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal-fetal interface. In eLife, 13, . doi:10.7554/eLife.100002. https://pubmed.ncbi.nlm.nih.gov/40152904/

9. Huang, Chen, Wang, Yuqin, Lin, Xiao, Lai, Keng Po, Li, Rong. 2022. Uncovering the functions of plasma proteins in ulcerative colitis and identifying biomarkers for BPA-induced severe ulcerative colitis: A plasma proteome analysis. In Ecotoxicology and environmental safety, 242, 113897. doi:10.1016/j.ecoenv.2022.113897. https://pubmed.ncbi.nlm.nih.gov/35999755/