PloS one, 2008-02, Vol.3 (2), p.e1576-e1576
2008
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- Autor(en) / Beteiligte
- Titel
- HLA-DR alpha 2 mediates negative signalling via binding to Tirc7 leading to anti-inflammatory and apoptotic effects in lymphocytes in vitro and in vivo
- Ist Teil von
- PloS one, 2008-02, Vol.3 (2), p.e1576-e1576
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2008
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-zeta chain & ZAP70, and inhibition of IFN-gamma and FasL expression. HLA-DRalpha2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRalpha2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0001576Titel-ID: cdi_plos_journals_1312187033
- Format
- –
- Schlagworte
- Anti-inflammatory agents, Antigen presentation, Antigen-presenting cells, Antigens, Apoptosis, CD4 antigen, CD4-Positive T-Lymphocytes - cytology, CD4-Positive T-Lymphocytes - immunology, CD8 antigen, Cell activation, Cell Biology/Cell Signaling, Cell growth, Cell Proliferation, Cells, Cultured, Cytokines, FasL protein, Histocompatibility antigen HLA, HLA-DR Antigens - metabolism, Humans, Immunology, Immunology/Autoimmunity, Immunology/Immune Response, Immunology/Immunomodulation, Immunology/Leukocyte Activation, Inflammation, Inflammation - immunology, Inhibition, Interferon, Ligands, Lipopolysaccharides, Lymphocytes, Lymphocytes - cytology, Lymphocytes - immunology, Lymphocytes T, Peptides, Phosphorylation, Physiology, Proteins, Recruitment, Rodents, SHP-1 protein, Signal Transduction, Signaling, Stat4 protein, T cell receptors, T cells, T-cell receptor, Vacuolar Proton-Translocating ATPases - metabolism, Womens health, ZAP-70 protein, γ-Interferon