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Regulation of CD47 expression on CD14+ monocytes by interferon-α in PBC patients
Xi Su1,2, Wenwen Jin1,2, Lizhi Liu2
1Department of Laboratory Medicine, Hunan Provincial People's Hospital (the First- Affiliated Hospital of Hunan Normal University), Changsha, China.
Background:
Primary biliary cholangitis (PBC) is a chronic intrahepatic cholestatic autoimmune liver disease characterized by inflammatory injury of small and medium-sized bile ducts in the liver. The pathogenesis of PBC has yet to be entirely understood. CD47/signal-regulatory protein alpha (SIRPα) is closely related to developing autoimmune diseases by promoting inflammatory response. However, the effect of CD47/SIRPα on inflammatory response in PBC patients is still unclear.
Objective:
We investigated the expression of CD47/SIRPα and the effect of inflammatory cytokines on the CD47 expression, analyzed potential autoantibodies against CD47 and the effect of anti-CD47 antibody on the inflammatory response in PBC, provided laboratory basis for the study of the pathogenesis and targets for non-invasive diagnosis and treatment on PBC.
Methods:
The expression levels of CD47 and SIRPα on peripheral blood mononuclear cells (PBMC) were measured in 14 patients with PBC (the PBC group) and 13 healthy subjects (the Control group) by flow cytometry (FCM). The PBMC derived from healthy subjects were stimulated with healthy subjects' serum, PBC patients' serum, IFN-α or TNF-α, and the CD47 expression level on CD14+ monocytes was detected by FCM. The level of serum anti-CD47 antibody or IFN-α in PBC patients and healthy subjects was analyzed by ELISA. FCM was used to examine the TNF-α expression level in CD14+ monocytes of healthy subjects stimulated with isotype control antibody, anti-CD47 antibody, LPS or LPS combined with CD47 antibody.
Results:
The CD47 expression level on the CD14+ monocytes in PBC patients was statistically higher than that in the Control group (P<0.01). Compared with the Control group (PBMC+healthy serum), the CD47 expression on CD14+ monocyte stimulated with the PBC patients' serum (PBMC+PBC patients' serum) was increased (P<0.001); the CD47 expression on CD14+ monocyte stimulated with IFN-α (PBMC + IFN-α) increased gradually with the increased concentration of IFN-α (P<0.05). However, there was no similar trend on CD14+ monocyte stimulated with the TNF-α (PBMC+TNF-α) (P>0.05). The levels of serum anti-CD47 antibody and IFN-α in the PBC patients were higher than those in healthy subjects (P<0.05). The TNF-α expression level in CD14+ monocyte stimulated with the LPS (PBMC+LPS) or anti-CD47 antibody+LPS group (PBMC+LPS+anti-CD47 antibody) was significantly increased than that in the Control group (PBMC+isotype control antibody) (P<0.01 and P<0.001, respectively). The TNF-α expression level in CD14+ monocyte stimulated with the anti-CD47 antibody + LPS was higher than that with the LPS (P< 0.05).
Conclusion:
The CD47 may be related to the pathogenesis of PBC by inflammatory response. The CD47/SIRPα signal were imbalanced in PBC patients. The presence of serum anti-CD47 antibodies in PBC patients provides a laboratory basis for clinical diagnosis and treatment.
Insights
This study found elevated CD47 expression and anti-CD47 antibodies in primary biliary cholangitis (PBC) patients, suggesting CD47/SIRPα signaling imbalance contributes to PBC pathogenesis and offers diagnostic potential.
Area of Science:
- Immunology
- Hepatology
- Autoimmune Diseases
Background:
- Primary biliary cholangitis (PBC) is an autoimmune liver disease with unclear pathogenesis.
- The CD47/signal-regulatory protein alpha (SIRPα) pathway is implicated in autoimmune diseases by modulating inflammatory responses.
Purpose of the Study:
- To investigate CD47/SIRPα expression and its role in PBC pathogenesis.
- To explore the diagnostic potential of CD47-related markers in PBC.
Main Methods:
- Flow cytometry was used to measure CD47 and SIRPα expression on peripheral blood mononuclear cells (PBMCs) from PBC patients and healthy controls.
- PBMCs were stimulated with patient/healthy serum, IFN-α, or TNF-α to assess CD47 expression changes.
- ELISA was employed to quantify serum anti-CD47 antibodies and IFN-α levels.
- TNF-α expression was analyzed in monocytes stimulated with anti-CD47 antibody and LPS.
Main Results:
- CD47 expression was significantly higher on monocytes from PBC patients compared to controls.
- PBC patient serum and IFN-α increased CD47 expression on monocytes.
- Serum anti-CD47 antibodies and IFN-α levels were elevated in PBC patients.
- Anti-CD47 antibody enhanced LPS-induced TNF-α production in monocytes.
Conclusions:
- The CD47/SIRPα pathway is imbalanced in PBC and may contribute to disease pathogenesis through inflammatory mechanisms.
- Elevated CD47 expression and the presence of anti-CD47 antibodies in PBC patients suggest potential as biomarkers for diagnosis and therapeutic targets.
