CD5L, also known as CD5 molecule-like, apoptosis inhibitor of macrophage (AIM), or Spα, is a secreted glycoprotein. It plays a crucial role in inflammatory responses, participating in processes such as infection, atherosclerosis, and cancer [1,2,3,4,5,6,7]. It is involved in pathways like autophagy, cell polarization, and lipid metabolism regulation, which are essential for maintaining normal physiological functions [1,7]. Genetic models, such as gene knockout (KO) mouse models, can be valuable for studying CD5L.

In macrophage studies, CD5L promotes M2 macrophage polarization through autophagy-mediated upregulation of ID3. In CD5L-deficient mice, neutrophil recruitment and bacterial control are impaired, making them more susceptible to experimental sepsis [1,4]. In cancer, high TAM expression of CD5L in papillary lung adenocarcinoma is associated with poor patient outcome, and anti-CD5L mAb can inhibit tumor progression by altering the tumor microenvironment [2]. In renal fibrosis, CD5L up-regulates the TGF-β signaling pathway, and its antibody can reduce the degree of renal fibrosis in UUO mice [5].

In conclusion, CD5L is a key immune effector involved in multiple biological processes. Model-based research, especially KO mouse models, has revealed its significant roles in various disease areas, including sepsis, cancer, and renal fibrosis. Understanding CD5L can potentially lead to new therapeutic strategies for these diseases.

References:

1. Sanjurjo, Lucía, Aran, Gemma, Téllez, Érica, Prats, Clara, Sarrias, Maria-Rosa. 2018. CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3. In Frontiers in immunology, 9, 480. doi:10.3389/fimmu.2018.00480. https://pubmed.ncbi.nlm.nih.gov/29593730/

2. Sanchez-Moral, Lidia, Paul, Tony, Martori, Clara, Kremer, Leonor, Sarrias, Maria-Rosa. 2023. Macrophage CD5L is a target for cancer immunotherapy. In EBioMedicine, 91, 104555. doi:10.1016/j.ebiom.2023.104555. https://pubmed.ncbi.nlm.nih.gov/37054630/

3. LaFargue, Christopher J, Amero, Paola, Noh, Kyunghee, An, Zhiqiang, Sood, Anil K. 2023. Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L. In Nature communications, 14, 2407. doi:10.1038/s41467-023-36910-5. https://pubmed.ncbi.nlm.nih.gov/37100807/

4. Oliveira, Liliana, Silva, M Carolina, Gomes, Ana P, Mallo, Moisés, Carmo, Alexandre M. 2024. CD5L as a promising biological therapeutic for treating sepsis. In Nature communications, 15, 4119. doi:10.1038/s41467-024-48360-8. https://pubmed.ncbi.nlm.nih.gov/38750020/

5. Chen, Chao, Feng, Chen, Luo, Qiulin, Qi, Zhongquan, Dai, Helong. 2024. CD5L up-regulates the TGF-β signaling pathway and promotes renal fibrosis. In Life sciences, 354, 122945. doi:10.1016/j.lfs.2024.122945. https://pubmed.ncbi.nlm.nih.gov/39127319/

6. Yang, Huiqing, Luo, Yan, Lai, Xiaofei. 2024. CD5L induces inflammation and survival in RA-FLS through ERK1/2 MAPK pathway. In Autoimmunity, 57, 2201412. doi:10.1080/08916934.2023.2201412. https://pubmed.ncbi.nlm.nih.gov/38425093/

7. Sanchez-Moral, Lidia, Ràfols, Neus, Martori, Clara, Téllez, Érica, Sarrias, Maria-Rosa. 2021. Multifaceted Roles of CD5L in Infectious and Sterile Inflammation. In International journal of molecular sciences, 22, . doi:10.3390/ijms22084076. https://pubmed.ncbi.nlm.nih.gov/33920819/