TY  - JOUR
A1  - Hollmann, Claudia
A1  - Wiese, Teresa
A1  - Dennstädt, Fabio
A1  - Fink, Julian
A1  - Schneider-Schaulies, Jürgen
A1  - Beyersdorf, Niklas
T1  - Translational approaches targeting ceramide generation from sphingomyelin in T cells to modulate immunity in humans
JF  - Frontiers in Immunology
N2  - In T cells, as in all other cells of the body, sphingolipids form important structural components of membranes. Due to metabolic modifications, sphingolipids additionally play an active part in the signaling of cell surface receptors of T cells like the T cell receptor or the co-stimulatory molecule CD28. Moreover, the sphingolipid composition of their membranes crucially affects the integrity and function of subcellular compartments such as the lysosome. Previously, studying sphingolipid metabolism has been severely hampered by the limited number of analytical methods/model systems available. Besides well-established high resolution mass spectrometry new tools are now available like novel minimally modified sphingolipid subspecies for click chemistry as well as recently generated mouse mutants with deficiencies/overexpression of sphingolipid-modifying enzymes. Making use of these tools we and others discovered that the sphingolipid sphingomyelin is metabolized to ceramide to different degrees in distinct T cell subpopulations of mice and humans. This knowledge has already been translated into novel immunomodulatory approaches in mice and will in the future hopefully also be applicable to humans. In this paper we are, thus, summarizing the most recent findings on the impact of sphingolipid metabolism on T cell activation, differentiation, and effector functions. Moreover, we are discussing the therapeutic concepts arising from these insights and drugs or drug candidates which are already in clinical use or could be developed for clinical use in patients with diseases as distant as major depression and chronic viral infection.
KW  - sphingolipids
KW  - CD4+ T cells
KW  - regulatory T cells (Treg)
KW  - CD8+ T cells
KW  - anti-depressant drug
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198806
SN  - 1664-3224
VL  - 10
IS  - 2363
ER  -