Cd209a, also known as SIGNR5 and a murine homolog of human DC-specific ICAM-3-grabbing nonintegrin, is a C-type lectin receptor (CLR). It is involved in the regulation of immune responses, playing a role in the activation of dendritic cells (DCs) and macrophages, and is associated with pathways like Raf-1 activation [1,2,3,4]. Its function is crucial in the context of various immune-related biological processes and diseases [1,2,3,4]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In schistosomiasis, CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments egg-induced IL-1β and IL-23 production initiated by Dectin-2 and Mincle [1]. CD209a-expressing macrophages mediate the beneficial effect of LECT2 on bacterial sepsis, as LECT2 treatment could enhance phagocytosis and bacterial killing of macrophages via CD209a [5]. Also, in Helicobacter pylori-infected bone marrow-derived dendritic cells (BMDCs), CD209a mediates LECT2-induced maturation and cytokine secretion of DCs through the CD209a-JNK/P38 MAPK pathway [2].

In conclusion, Cd209a is essential for the development of pathogenic Th17 cell-mediated immunopathology in schistosomiasis, and it is involved in the modulation of immune responses in bacterial infections like sepsis and Helicobacter pylori infection. The study of Cd209a using KO mouse models has revealed its key role in these specific disease-related immune processes, contributing to our understanding of the underlying immunological mechanisms [1,2,5].

References:

1. Kalantari, Parisa, Morales, Yoelkys, Miller, Emily A, Bunnell, Stephen C, Stadecker, Miguel J. . CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology. In Cell reports, 22, 1288-1300. doi:10.1016/j.celrep.2018.01.001. https://pubmed.ncbi.nlm.nih.gov/29386115/

2. Zhang, Xiaofen, Sun, Kefang, Tang, Chenxi, Yu, Chaohui, Li, Lan. 2023. LECT2 modulates dendritic cell function after Helicobacter pylori infection via the CD209a receptor. In Journal of gastroenterology and hepatology, 38, 625-633. doi:10.1111/jgh.16138. https://pubmed.ncbi.nlm.nih.gov/36740832/

3. Ponichtera, Holly E, Shainheit, Mara G, Liu, Beiyun C, Hacohen, Nir, Stadecker, Miguel J. 2014. CD209a expression on dendritic cells is critical for the development of pathogenic Th17 cell responses in murine schistosomiasis. In Journal of immunology (Baltimore, Md. : 1950), 192, 4655-65. doi:10.4049/jimmunol.1400121. https://pubmed.ncbi.nlm.nih.gov/24729611/

4. Kalantari, Parisa, Bunnell, Stephen C, Stadecker, Miguel J. 2019. The C-type Lectin Receptor-Driven, Th17 Cell-Mediated Severe Pathology in Schistosomiasis: Not All Immune Responses to Helminth Parasites Are Th2 Dominated. In Frontiers in immunology, 10, 26. doi:10.3389/fimmu.2019.00026. https://pubmed.ncbi.nlm.nih.gov/30761125/

5. Lu, Xin-Jiang, Chen, Jiong, Yu, Chao-Hui, Zhang, Shun, Xu, Lei. 2012. LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor. In The Journal of experimental medicine, 210, 5-13. doi:10.1084/jem.20121466. https://pubmed.ncbi.nlm.nih.gov/23254286/