Refine
Has Fulltext
- yes (28)
Is part of the Bibliography
- yes (28)
Year of publication
Document Type
- Journal article (18)
- Doctoral Thesis (9)
- Habilitation (1)
Keywords
- regulatory T cells (28) (remove)
Institute
- Institut für Virologie und Immunbiologie (12)
- Neurologische Klinik und Poliklinik (4)
- Graduate School of Life Sciences (3)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (3)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (2)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (2)
- Kinderklinik und Poliklinik (2)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (2)
- Medizinische Klinik und Poliklinik I (2)
- Medizinische Klinik und Poliklinik II (2)
Sonstige beteiligte Institutionen
Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3\(^+\) regulatory T-cell frequencies among CD4\(^+\) T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4\(^+\) Foxp3\(^+\) regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3\(^+\) regulatory T cell among human CD4\(^+\) T cells in vitro. In an observational prospective clinical study with patients suffering from major depression, we observed that acid sphingomyelinase-inhibiting antidepressants induced a stronger relative increase in the frequency of CD4\(^+\) Foxp3\(^+\) regulatory T cells in peripheral blood than acid sphingomyelinase-non- or weakly inhibiting antidepressants. This was particularly true for CD45RA\(^-\) CD25\(^{high}\) effector CD4\(^+\) Foxp3\(^+\) regulatory T cells. Mechanistically, our data indicate that the positive effect of acid sphingomyelinase inhibition on CD4\(^+\) Foxp3\(^+\) regulatory T cells required CD28 co-stimulation, suggesting that enhanced CD28 co-stimulation was the driver of the observed increase in the frequency of Foxp3+ regulatory T cells among human CD4\(^+\) T cells. In summary, the widely induced pharmacological inhibition of acid sphingomyelinase activity in patients leads to an increase in Foxp3+ regulatory T-cell frequencies among CD4\(^+\) T cells in humans both in vivo and in vitro.