Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy

Area of Science:

• Immunology
• Cardiology

Background:

• Chronic immune activation is implicated in dilated cardiomyopathy (DCM) pathogenesis.
• CD4(+) LAP(+) Tregs are a recently identified T cell subset with immune-suppressive functions.

Purpose of the Study:

• To investigate the frequency and function of circulating CD4(+) LAP(+) Tregs in DCM patients.
• To determine if CD4(+) LAP(+) Tregs are impaired in DCM and contribute to disease mechanisms.

Main Methods:

• Flow cytometry was used to quantify circulating CD4(+) LAP(+) Tregs.
• In vitro assays assessed the suppressive function of CD4(+) LAP(+) Tregs on T and B cell proliferation and B cell IgG production.
• Correlation analyses examined relationships between Treg frequency and clinical parameters (LVEF, NT-proBNP, IgG3).

Main Results:

• DCM patients exhibited significantly lower frequencies of circulating CD4(+) LAP(+) Tregs compared to healthy controls.
• CD4(+) LAP(+) Tregs from DCM patients demonstrated compromised suppressive function against T and B cell proliferation and B cell IgG production.
• CD4(+) LAP(+) Treg frequency positively correlated with LVEF and negatively with serum IgG3 and NT-proBNP levels.

Conclusions:

• The frequency of CD4(+) LAP(+) Tregs is reduced, and their suppressive function is impaired in DCM patients.
• Defective CD4(+) LAP(+) Tregs may represent a key mechanism underlying immune activation in DCM.
• These findings highlight a potential role for CD4(+) LAP(+) Tregs in DCM pathogenesis and suggest them as a therapeutic target.