Cd1d1, an ortholog of human CD1d, is a non-classical class I-like major histocompatibility complex molecule. It mainly participates in lipid-antigen presentation to invariant natural killer T (NKT) cells, playing a crucial role in the development and function of this unique subset of immunoregulatory T cells [2,3]. CD1d1-mediated TCR signals integrate with other intrinsic signals to influence strain-specific NKT cell differentiation programs and subset distributions [1].

In macrophage-specific CD1d1-deficient (LymCD1d1-/-) mice, resistance to dextran sodium sulfate (DSS)-induced colitis is acquired due to transcriptional inhibition of NLRP3 inflammasome components [2]. CD1d1-deficient (CD1KO) mice, lacking NKT cells, produce significantly higher amounts of IL-2, IL-4, and IFN-γ compared with wild-type controls after lymphocytic choriomeningitis virus infection, indicating that CD1d1 expression controls the magnitude of the cell-mediated immune response to an acute viral infection [4]. Mice with dendritic cell-specific deletion of the autophagy gene Atg5 show enhanced CD1D1-restricted glycolipid presentation, leading to increased iNKT cell cytokine production [5].

In conclusion, Cd1d1 is essential for lipid-antigen presentation to NKT cells, influencing NKT cell differentiation and function. Gene-knockout mouse models have revealed its significant role in inflammatory bowel diseases, as seen in DSS-induced colitis, and in the control of the magnitude of the acute antiviral immune response. These findings provide insights into potential intervention strategies for treating inflammatory disorders and understanding the immune response to viral infections.

References:

1. Amable, Ludivine, Ferreira Martins, Luis Antonio, Pierre, Remi, Klibi, Jihene, Benlagha, Kamel. 2023. Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation. In Nature communications, 14, 7922. doi:10.1038/s41467-023-43424-7. https://pubmed.ncbi.nlm.nih.gov/38040679/

2. Cui, Shan, Wang, Chenhui, Bai, Weizhi, Wu, Yuzhang, Chen, Yongwen. 2020. CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation. In Science advances, 6, . doi:10.1126/sciadv.aaz7290. https://pubmed.ncbi.nlm.nih.gov/33087357/

3. Geng, Yanbiao, Laslo, Peter, Barton, Kevin, Wang, Chyung-Ru. . Transcriptional regulation of CD1D1 by Ets family transcription factors. In Journal of immunology (Baltimore, Md. : 1950), 175, 1022-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16002702/

4. Roberts, Tonya J, Lin, Yinling, Spence, Philip M, Van Kaer, Luc, Brutkiewicz, Randy R. . CD1d1-dependent control of the magnitude of an acute antiviral immune response. In Journal of immunology (Baltimore, Md. : 1950), 172, 3454-61. doi:. https://pubmed.ncbi.nlm.nih.gov/15004145/

5. Keller, Christian W, Loi, Monica, Ewert, Svenja, Freigang, Stefan, Lünemann, Jan D. 2017. The autophagy machinery restrains iNKT cell activation through CD1D1 internalization. In Autophagy, 13, 1025-1036. doi:10.1080/15548627.2017.1297907. https://pubmed.ncbi.nlm.nih.gov/28296542/