Human CD22 Stable Cell Line - HEK293T

CD22 has been implicated in neuroinflammatory diseases such as Alzheimer's disease (AD). Specifically, plasma soluble CD22 (sCD22) level is upregulated in patients with AD. Here, researchers report that sCD22 promotes neuroinflammation both in vivo and in vitro. sCD22 activates microglia via p38 and ERK1/2 signaling pathways, leading to the secretion of TNFα, IL-6, and CCL3. In addition, sCD22 activates microglia via its sialic acid binding domain and 2,6-linked sialoglycans on sCD22. Targeting CD22 has critical therapeutic potential in amyloid-β (Aβ)-induced neuroinflammation in hCD22 transgenic mice. Suciraslimab improves working memory and alleviates neuroinflammation in vivo. Furthermore, membrane CD22 inhibited the amyloid β protein (Aβ)-induced NFκB signaling pathway, and mechanistic studies showed that suciraslimab inhibited Aβ-induced IL-1β secretion in human microglia and peripheral blood mononuclear cells (PBMCs). Suciraslimab also inhibited the secretion of IL-12 and IL-23 in human peripheral blood mononuclear cells (PBMCs). In addition, suciraslimab reduced the expression of α4 integrin on the surface of B cells. Interestingly, CD22 interacts with Aβ, and suciraslimab enhances the internalization of CD22-Aβ complexes in microglia. These data highlight the importance of sCD22 in driving neuroinflammation and the dual mechanism of targeting CD22 to alleviate Aβ-induced inflammation and promote Aβ phagocytosis.

Both mouse and human recombinant CD22 were found to interact with Aβ, forming CD22-Aβ complexes with significant affinity, as shown by biolayer interferometry studies (Figure 1A and B). Next, the researchers tested whether CD22 expression on the cell surface interacts with Aβ. They generated HEK293 cells overexpressing human CD22. The cells were immunostained with FITC-conjugated Aβ. The results showed that the FITC signal was significantly enhanced in human CD22 overexpressing HEK293 cells compared to HEK293 cells, indicating an interaction between membrane CD22 and Aβ (Figure 1C). In addition, the researchers tested whether endogenous CD22 expression in human microglia is sufficient for interaction with Aβ. Aβ was incubated with HMC-3 in culture, and the CD22-Aβ interaction was examined using a proximity ligation assay. CD22-Aβ interaction was detected using anti-CD22 antibody/anti-Aβ antibody pair or IgG control/anti-Aβ antibody pair. In HMC-3 cells, the PLA signal of the anti-CD22 antibody/anti-Aβ antibody pair group was significantly higher than that of the control pair (Figure 1D). Both mouse and human CD22 extracellular domains (ECDs) interact with Aβ. The two ECDs were structurally aligned and found to have high TM scores, indicating that they have high structural similarity (Figure 1E). Further splitting of the individual domains to examine the sequence similarity revealed that domain 6 (76.2%) and domain 7 (82.1%) had higher sequence similarity, suggesting that these two domains may be critical for the interaction with Aβ.

Figure 1. Suciraslimab promotes Aβ phagocytosis. (Mai Y D, et al., 2025)