title: Aldose reductase participates in the downregulation of T cell functions due to suppressor macrophages.
abstract: The cell-to-cell contact of T lymphocytes with immunosuppressive macrophages causes marked changes in the tyrosine phosphorylation of some cytosolic proteins of T cells. By phosphoproteome analysis, we identified a 36-kDa protein as aldose reductase (AR). The AR expression in T cells was not changed by TCR stimulation or due to cell-to-cell transmission of suppressor signals from immunosuppressive macrophages. Therefore, AR phosphorylation/dephosphorylation is essential for the transduction of TCR-mediated T-cell stimulatory signals, and moreover plays important roles for the cross-talk of immunosuppressive macrophage-derived suppressor signals with the signaling pathways for T-cell activation. Moreover, AR played important roles in the upregulation of ERK1/2-mediated signaling pathways in T lymphocytes. Notably, the enzymatic activity of AR was not required for its signaling action. Taken together, it is concluded that AR mediates intracellular transmission of the suppressor signal of immunosuppressive macrophages toward downstream ERK1/2 pathways, possibly through its direct interaction with acceptor proteins.
authors: Department of Nutritional Sciences, Yasuda Women's University, Hiroshima 731-0153, Japan.
authors: Toshiaki
authors: T
authors: Shimizu
authors: Department of Pharmaceutical Sciences, International University of Health and Welfare, Ohtawara 324-8501, Japan.
authors: Yutaka
authors: Y
authors: Tatano
authors: Department of Basic Medical Sciences for Nursing, Yasuda Women's University, Hiroshima 731-0153, Japan.|Department of Microbiology and Immunology, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors: Haruaki
authors: H
authors: Tomioka
mesh_terms: D000449:Aldehyde Reductase / Q000276:immunology*; D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D000449:Aldehyde Reductase; D048052:Mitogen-Activated Protein Kinase 3