Ccr3, also known as CD193 and C-C chemokine receptor type 3, is a G-protein coupled receptor. It plays a crucial role in inflammatory, autoimmune, and neuronal migration mechanisms. Ligands like eotaxins, RANTES, MCP-3, and MCP-4 bind to Ccr3, and it is involved in pathways related to allergic responses, with its activation triggering downstream cascades in related inflammatory cells [1,3,5,7]. It is expressed on various cell types including eosinophils, basophils, mast cell subpopulations, activated Th2 cells, macrophages, airway epithelial cells, and B cells [7,8].

In male mice lacking Ccr3, there is a disturbed bone remodeling leading to a cortical bone phenotype with thin femoral cortical bone, reduced cortical bone volume and thickness, and increased periosteal mineralization. This suggests that Ccr3 has a sex-related role in bone modeling, potentially regulated by sex hormones. However, female mice do not exhibit this skeletal phenotype [4]. In respiratory allergic diseases such as asthma and allergic rhinitis, Ccr3 is an important target gene. The related inflammatory cells respond to Ccr3 activation, causing allergic inflammation [1]. Blocking Ccr3 has been proposed as a therapy for asthma as it may inhibit eosinophil trafficking and T-cell recruitment into the airways [5,7]. In Down syndrome patients, Ccr3 gene is over-expressed, suggesting its association with the phenotype of these patients [2]. Also, in carcinoma cell lines, blocking Ccr3 induced polyploidization associated with epithelial-mesenchymal transition processes [6]. A meta-analysis indicated that the Ccr3 rs6441961 polymorphism may be a risk factor for celiac disease in European populations [9]. In paediatric schistosomiasis, CD193 (CCR3) expression by B cells correlates with reduced IgE production [8].

In summary, Ccr3 is involved in multiple biological processes and disease conditions. Mouse models, especially those with Ccr3 deficiency, have revealed its sex-specific role in bone remodeling. In diseases like respiratory allergies, asthma, Down syndrome, carcinoma, celiac disease, and paediatric schistosomiasis, Ccr3 plays significant roles, whether through its involvement in inflammatory responses, cell trafficking, or gene expression regulation. Understanding Ccr3's function provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Tang, Saiyi, Shu, Xinhua. . [Effect of CCR3 gene on related inflammatory cells in respiratory allergic diseases]. In Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery, 35, 80-84. doi:10.13201/j.issn.2096-7993.2021.01.021. https://pubmed.ncbi.nlm.nih.gov/33540982/

2. Salemi, Michele, Cannarella, Rossella, Marchese, Giovanna, Calogero, Aldo E, Romano, Corrado. 2021. CCR3 gene overexpression in patients with Down syndrome. In Molecular biology reports, 48, 5335-5338. doi:10.1007/s11033-021-06503-w. https://pubmed.ncbi.nlm.nih.gov/34184200/

3. Gangur, Venu, Birmingham, Neil P, Thanesvorakul, Sirinart, Joseph, Shama. . CCR3 and CXCR3 as drug targets for allergy: principles and potential. In Current drug targets. Inflammation and allergy, 2, 53-62. doi:. https://pubmed.ncbi.nlm.nih.gov/14561176/

4. Rosendahl, Sara, Sulniute, Rima, Persson, Julia, Kindstedt, Elin, Lundberg, Pernilla. 2022. Lack of CCR3 leads to a skeletal phenotype only in male mice. In Biochemical and biophysical research communications, 620, 98-104. doi:10.1016/j.bbrc.2022.06.062. https://pubmed.ncbi.nlm.nih.gov/35780587/

5. Bertrand, C P, Ponath, P D. . CCR3 blockade as a new therapy for asthma. In Expert opinion on investigational drugs, 9, 43-52. doi:. https://pubmed.ncbi.nlm.nih.gov/11060659/

6. Kaibori, Yuichiro, Nagakubo, Daisuke. 2022. CCR3 blockage elicits polyploidization associated with the signatures of epithelial-mesenchymal transition in carcinoma cell lines. In Cancer gene therapy, 30, 137-148. doi:10.1038/s41417-022-00532-8. https://pubmed.ncbi.nlm.nih.gov/36123391/

7. Erin, E M, Williams, T J, Barnes, P J, Hansel, T T. . Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. In Current drug targets. Inflammation and allergy, 1, 201-14. doi:. https://pubmed.ncbi.nlm.nih.gov/14561201/

8. Onkanga, I O, Sang, H, Hamilton, R, Odiere, M R, Ganley-Leal, L. 2023. CD193 (CCR3) expression by B cells correlates with reduced IgE production in paediatric schistosomiasis. In Parasite immunology, 45, e12979. doi:10.1111/pim.12979. https://pubmed.ncbi.nlm.nih.gov/36971331/

9. Yang, Guang, Zhang, Baohuan, Huang, Weihuang, Wei, Xiangcai, Jing, Chunxia. 2015. Systematic review and meta-analysis of the association between IL18RAP rs917997 and CCR3 rs6441961 polymorphisms with celiac disease risks. In Expert review of gastroenterology & hepatology, 9, 1327-38. doi:10.1586/17474124.2015.1075880. https://pubmed.ncbi.nlm.nih.gov/26289103/