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Abstract
Chronic inflammatory T-cell-mediated diseases such as inflammatory bowel disease (IBD) are often treated with immunosuppressants including corticosteroids. In addition to the intended T-cell suppression, these farmacons give rise to many side effects. Recently, immunosuppressive phospholipids have been proposed as less-toxic alternatives. We aimed to investigate the immunoregulatory capacities of the naturally occurring phospholipid phosphatidylinositol (PI). Systemic PI treatment dramatically reduced disease severity and intestinal inflammation in murine 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Moreover, PI treatment inhibited the inflammatory T-cell response in these mice, as T cells derived from colon-draining LN of PI-treated mice secreted less IL-17 and IFN-gamma upon polyclonal restimulation when compared to those of saline-treated mice. Further characterization of the suppressive capacity of PI revealed that the phospholipid suppressed Th cell differentiation in vitro irrespective of their cytokine profile by inhibiting proliferation and IL-2 release. In particular, PI diminished IL-2 mRNA expression and inhibited ERK1-, ERK-2-, p38- and JNK-phosphorylation. Crucially, PI did not ablate Treg differentiation or the antigen-presenting capacity of DCs in vitro. These data validate PI as a pluripotent inhibitor that can be applied mucosally as well as systemically. Its compelling functions render PI a promising novel physiological immune suppressant.
Keywords
Immune suppression, Inflammatory bowel disease, PHOSPHATIDYLCHOLINE, REGULATORY T-CELLS, TNBS-INDUCED COLITIS, TRANSFER PROTEIN-ALPHA, INFLAMMATORY-BOWEL-DISEASE, T cells, Regulation, Phospholipids, MODEL, SUPPRESSION, INDUCTION, TOLERANCE, INTESTINE

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Citation

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Chicago
van Dieren, Jolanda M, Ytje Simons-Oosterhuis, HC (Rolien) Raatgeep, Dicky J Lindenbergh-Kortleve, Margaretha EH Lambers, C Janneke van der Woude, Ernst J Kuipers, et al. 2011. “Anti-inflammatory Actions of Phosphatidylinositol.” European Journal of Immunology 41 (4): 1047–1057.
APA
van Dieren, J. M., Simons-Oosterhuis, Y., Raatgeep, H. (Rolien), Lindenbergh-Kortleve, D. J., Lambers, M. E., van der Woude, C. J., Kuipers, E. J., et al. (2011). Anti-inflammatory actions of phosphatidylinositol. EUROPEAN JOURNAL OF IMMUNOLOGY, 41(4), 1047–1057.
Vancouver
1.
van Dieren JM, Simons-Oosterhuis Y, Raatgeep H (Rolien), Lindenbergh-Kortleve DJ, Lambers ME, van der Woude CJ, et al. Anti-inflammatory actions of phosphatidylinositol. EUROPEAN JOURNAL OF IMMUNOLOGY. 2011;41(4):1047–57.
MLA
van Dieren, Jolanda M, Ytje Simons-Oosterhuis, HC (Rolien) Raatgeep, et al. “Anti-inflammatory Actions of Phosphatidylinositol.” EUROPEAN JOURNAL OF IMMUNOLOGY 41.4 (2011): 1047–1057. Print.
@article{1996980,
  abstract     = {Chronic inflammatory T-cell-mediated diseases such as inflammatory bowel disease (IBD) are often treated with immunosuppressants including corticosteroids. In addition to the intended T-cell suppression, these farmacons give rise to many side effects. Recently, immunosuppressive phospholipids have been proposed as less-toxic alternatives. We aimed to investigate the immunoregulatory capacities of the naturally occurring phospholipid phosphatidylinositol (PI). Systemic PI treatment dramatically reduced disease severity and intestinal inflammation in murine 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Moreover, PI treatment inhibited the inflammatory T-cell response in these mice, as T cells derived from colon-draining LN of PI-treated mice secreted less IL-17 and IFN-gamma upon polyclonal restimulation when compared to those of saline-treated mice. Further characterization of the suppressive capacity of PI revealed that the phospholipid suppressed Th cell differentiation in vitro irrespective of their cytokine profile by inhibiting proliferation and IL-2 release. In particular, PI diminished IL-2 mRNA expression and inhibited ERK1-, ERK-2-, p38- and JNK-phosphorylation. Crucially, PI did not ablate Treg differentiation or the antigen-presenting capacity of DCs in vitro. These data validate PI as a pluripotent inhibitor that can be applied mucosally as well as systemically. Its compelling functions render PI a promising novel physiological immune suppressant.},
  author       = {van Dieren, Jolanda M and Simons-Oosterhuis, Ytje and Raatgeep, HC (Rolien) and Lindenbergh-Kortleve, Dicky J and Lambers, Margaretha EH and van der Woude, C Janneke and Kuipers, Ernst J and Snoek, Gerry T and Potman, Ron and Hammad, Hamida and Lambrecht, Bart and Samsom, Janneke N and Nieuwenhuis, Edward ES},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keyword      = {Immune suppression,Inflammatory bowel disease,PHOSPHATIDYLCHOLINE,REGULATORY T-CELLS,TNBS-INDUCED COLITIS,TRANSFER PROTEIN-ALPHA,INFLAMMATORY-BOWEL-DISEASE,T cells,Regulation,Phospholipids,MODEL,SUPPRESSION,INDUCTION,TOLERANCE,INTESTINE},
  language     = {eng},
  number       = {4},
  pages        = {1047--1057},
  title        = {Anti-inflammatory actions of phosphatidylinositol},
  url          = {http://dx.doi.org/10.1002/eji.201040899},
  volume       = {41},
  year         = {2011},
}

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