ArticlePloS one2008
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.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Evolutionarily conserved amino acids in MHC-II mediate bat influenza A virus entry into human cells.PLoS biology · 2023Article
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- Immune Regulatory 1 Cells: A Novel and Potent Subset of Human T Regulatory Cells.Frontiers in immunology · 2021Article
- Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord.PloS one · 2016Article
- Transcriptome analysis of monocyte-HIV interactions.Retrovirology · 2010Article
- Cathepsin S regulates class II MHC processing in human CD4+ HLA-DR+ T cells.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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