title: Retinoic acid modulates interferon-γ production by hepatic natural killer T cells via phosphatase 2A and the extracellular signal-regulated kinase pathway.
abstract: Retinoic acid (RA), an active metabolite converted from vitamin A, plays an active role in immune function, such as defending against infections and immune regulation. Although RA affects various types of immune cells, including antigen-presenting cells, B lymphocytes, and T lymphocytes, whether it affects natural killer T (NKT) cells remain unknown. In this study, we found that RA decreased interferon (IFN)-γ production by activated NKT cells through T-cell receptor (TCR) and CD28. We also found that RA reduced extracellular signal-regulated kinase (ERK) phosphorylation, but increased phosphatase 2A (PP2A) activity in TCR/CD28-stimulated NKT cells. The increased PP2A activity, at least partly, contributed to the reduction of ERK phosphorylation. Since inhibition of ERK activation decreases IFN-γ production by TCR/CD28-stimulated NKT cells, RA may downregulate IFN-γ production by TCR/CD28-stimulated NKT cells through the PP2A-ERK pathway. Our results demonstrated a novel function of RA in modulating the IFN-γ expression by activated NKT cells.
authors.affiliation: 1 Genomics Research Center , Academia Sinica, Taipei, Taiwan .
authors.forename: Heng-Kwei
authors.initials: HK
authors.lastname: Chang
authors.forename: Wu-Shiun
authors.initials: WS
authors.lastname: Hou
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D014212:Tretinoin; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2