In vitro Conversion into CD4+CD25+Foxp3+ Induced Regulatory T Cells Is Reduced in Atopic Dermatitis Patients.

BACKGROUND

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-β signaling is compromised in regulatory T cells (Tregs).

OBJECTIVES

This study aimed to investigate the TGF-β-dependent in vitro conversion of CD4+CD25- T cells derived from AD-patients into CD4+CD25+Foxp3+ induced Tregs (iTregs) in comparison to healthy controls.

METHODS

To analyze in vitro iTreg conversion, human CD4+CD25- T cells were cultured on anti-CD3-coated plates in the presence of TGF-β and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4+CD25+Foxp3+ iTreg generation was explored by focusing on TGF-β signaling. Finally, the functionality of iTregs was investigated.

RESULTS

Conversion of CD4+CD25-Foxp3- into CD4+CD25+Foxp3+ iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4+CD25- T cells. Interestingly, the suppressive quality of iTregs was found to be equal in cells derived from AD and healthy donors.

CONCLUSION

The signaling effect of TGF-β receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.