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The Journal of Immunology, 2003, 170: 6033-6039.
Copyright © 2003 by The American Association of Immunologists

Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation1

Maximilian Zeyda*, Andreas B. Szekeres{dagger}, Marcus D. Säemann{dagger}, René Geyeregger*, Hannes Stockinger{dagger}, Gerhard J. Zlabinger{dagger}, Werner Waldhäusl*,{ddagger} and Thomas M. Stulnig2,*,{ddagger}

* Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism and {dagger} Institute of Immunology, University of Vienna Medical School, Vienna, Austria; and {ddagger} CeMM–Center of Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

Polyunsaturated fatty acids (PUFAs) are known to suppress inflammatory and autoimmune responses and, therefore, clinical applications of PUFAs as immunomodulatory substances are extensively studied. PUFAs are known to inhibit T cell responses, but with respect to TCR/CD3-mediated signal transduction only a block in CD3-induced phospholipase C{gamma}1/calcium signaling has been shown so far. In this study, we investigated PUFA-mediated changes in downstream T cell signal transduction. We show that among the mitogen-activated protein kinase families activation of c-Jun NH2-terminal kinase, but not phosphorylation of extracellular signal-regulated kinase-1/-2 or p38 is inhibited. CD3/CD28-induced activity of NF-AT was markedly reduced by PUFA treatment, while activation of other nuclear receptors (AP-1 and NF-{kappa}B) remained unaltered. Furthermore, IL-2 promoter activity, IL-2 and IL-13 mRNA levels, IL-2 secretion, and IL-2R {alpha}-chain expression were significantly diminished by PUFA treatment, whereas the expression of IFN-{gamma}, IL-4, IL-10, and CD69 remained essentially unaffected by PUFAs. In conclusion, PUFA treatment of T cells inhibits selectively c-Jun NH2-terminal kinase and NF-AT activation, resulting in diminished production of IL-2 and IL-13.




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