Cd84, also known as SLAMF5, is a member of the SLAM family of cell-surface immunoreceptors. It functions as a homophilic adhesion molecule. Its signaling can either activate or inhibit leukocyte function depending on cell type and activation/differentiation stage, regulating diverse immunological processes such as T cell cytokine secretion, natural killer cell cytotoxicity, monocyte activation, autophagy, T:B interactions, and B cell tolerance at the germinal center checkpoint [1].

In various disease models, Cd84 has been shown to play crucial roles. In chronic lymphocytic leukemia (CLL), blocking Cd84 in vitro and in vivo disrupts the interaction between CLL cells and their microenvironment, leading to cell death, suggesting it promotes CLL cell survival [2]. In multiple myeloma (MM), down-regulation or blocking of Cd84 reduces myeloid-derived suppressor cell (MDSC) accumulation, elevates T cell activity, and reduces tumor load, indicating its role in regulating the immunosuppressive microenvironment [3]. In Mycobacterium tuberculosis pathogenesis, Cd84-deficient mice showed improved M. tuberculosis clearance and longer survival, suggesting that Cd84 suppresses T and B cell activation during infection [4]. In acute myeloid leukemia (AML), down-regulation of Cd84 in human cell lines, patient-derived xenograft cells, and AML mouse models disrupted leukemia cell proliferation, clonogenicity, and engraftment, highlighting its role as a survival factor [5].

In conclusion, Cd84 is a key regulator in multiple immunological processes. Gene knockout (KO) or conditional knockout (CKO) mouse models have revealed its significance in diseases like CLL, MM, tuberculosis, and AML. These studies suggest that Cd84 could potentially be a therapeutic target in these disease areas, providing insights into disease mechanisms and possible treatment strategies.

References:

1. Cuenca, Marta, Sintes, Jordi, Lányi, Árpád, Engel, Pablo. 2018. CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and autoimmune disorders. In Clinical immunology (Orlando, Fla.), 204, 43-49. doi:10.1016/j.clim.2018.10.017. https://pubmed.ncbi.nlm.nih.gov/30522694/

2. Marom, A, Barak, A F, Kramer, M P, Herishanu, Y, Shachar, I. 2016. CD84 mediates CLL-microenvironment interactions. In Oncogene, 36, 628-638. doi:10.1038/onc.2016.238. https://pubmed.ncbi.nlm.nih.gov/27452524/

3. Lewinsky, Hadas, Gunes, Emine G, David, Keren, Rosen, Steven, Shachar, Idit. 2021. CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma. In JCI insight, 6, . doi:10.1172/jci.insight.141683. https://pubmed.ncbi.nlm.nih.gov/33465053/

4. Zheng, Nan, Fleming, Joy, Hu, Peilei, Bi, Lijun, Zhang, Hongtai. 2022. CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis. In Microbiology spectrum, 10, e0155721. doi:10.1128/spectrum.01557-21. https://pubmed.ncbi.nlm.nih.gov/35196822/

5. Zhu, Yinghui, Murtadha, Mariam, Liu, Miaomiao, Williams, John C, Pichiorri, Flavia. 2025. Identification of CD84 as a potent survival factor in acute myeloid leukemia. In The Journal of clinical investigation, , . doi:10.1172/JCI176818. https://pubmed.ncbi.nlm.nih.gov/40198133/