Panoply™ Human CD52 Over-expressing Stable Cell Line

Systemic sclerosis (SSc) is characterized by dysregulated type I interferon (IFN) signaling. CD52 is well known for its immunosuppressive function in T cells. Here, researchers investigated the role of CD52 in monocyte adhesion and type I IFN signaling in SSc patients. Pathway enrichment analysis revealed that adhesion- and type I IFN-related genes were increased in monocytes from SSc patients. These cells had upregulated CD11b/CD18 expression, decreased CD52 expression, and enhanced adhesion to intercellular adhesion molecule 1 and endothelial cells. Changes in CD52 expression were consistent with SSc subtypes as well as immunosuppressive therapy, autoantibody profiles, and monocyte adhesion properties in SSc patients. CD52 overexpression resulted in decreased levels of CD18 and monocyte adhesion, whereas CD52 knockdown increased monocyte adhesion. In blood samples from healthy controls, the humanized anti-CD52 monoclonal antibody alemtuzumab demonstrated increased monocyte adhesion and CD11b/CD18 expression and enhanced type I interferon responses. Monocyte CD52 expression is upregulated by interleukin-4 (IL-4)/IL-13 via the STAT6 pathway, whereas it is downregulated by lipopolysaccharide and interferons α, β, and γ in a JAK1- and histone deacetylase IIa (HDAC IIa)-dependent manner. Downregulation of the antiadhesive CD52 antigen in CD14+ monocytes represents a novel mechanism in the pathogenesis of systemic sclerosis (SSc).

Compared with control cells, CD52-overexpressing monocytes showed reduced adhesion levels to culture plates coated with ICAM1-Fc, ICAM2-Fc, and VCAM1-Fc, as well as to TNFα-activated endothelial cells (Figure 1A, B). Therefore, the researchers observed that monocyte adhesion to endothelial cells increased when CD52 expression was inhibited. Next, the microcapillary shear flow system was used to analyze the specific stages of monocyte adhesion to activated endothelial cells. The researchers observed no difference in the number and rolling distance of rolling cells between the two groups (Figure 1C). However, CD52-overexpressing cells rolled for a shorter time, at a faster speed, and with significantly fewer final adherents (Figure 1D).

Figure 1. CD52 expression modulates adhesion of THP-1 cell line. (Rudnik M, et al., 2021)