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p38 Mitogen-Activat...
p38 Mitogen-Activated Protein Kinase/Signal Transducer and Activator of Transcription-3 Pathway Signaling Regulates Expression of Inhibitory Molecules in T Cells Activated by HIV-1-Exposed Dendritic Cells
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- Che, Karlhans Fru (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Shankar, Esaki Muthu (author)
- University of Malaya, Malaysia
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- Muthu, Sundaram (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Zandi, Sasan (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Sigvardsson, Mikael (author)
- Linköpings universitet,Experimentell hematologi,Hälsouniversitetet
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- Hinkula, Jorma (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Messmer, Davorka (author)
- University of California, San Diego, United States
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- Larsson, Marie (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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(creator_code:org_t)
- 2012-07-03
- 2012
- English.
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In: Molecular Medicine. - : Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 18:8, s. 1169-1182
- Related links:
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https://doi.org/10.2...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
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- Human immunodeficiency virus type 1 (HIV-1) infection enhances the expression of inhibitory molecules on T cells, leading to T-cell impairment. The signaling pathways underlying the regulation of inhibitory molecules and subsequent onset of T-cell impairment remain elusive. We showed that both autologous and allogeneic T cells exposed to HIV-pulsed dendritic cells (DCs) upregulated cytotoxic T-lymphocyte antigen (CTLA-4), tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), lymphocyte-activation gene-3 (LAG3). T-cell immunoglobulin mucin-3 (TIM-3), CD160 and certain suppression-associated transcription factors, such as B-lymphocyte induced maturation protein-1 (BLIMP-1), deltex homolog 1 protein (DTX1) and forkhead box P3 (FOXP3), leading to T-cell suppression. This induction was regulated by p38 mitogen-activated protein kinase/signal transducer and activator of transcription-3 (P38MAPK/STAT3) pathways, because their blockade significantly abrogated expression of all the inhibitory molecules studied and a subsequent recovery in T-cell proliferation. Neither interleukin-6 (IL-6) nor IL-10 nor growth factors known to activate STAT3 signaling events were responsible for STAT3 activation. Involvement of the P38MAPK/STAT3 pathways was evident because these proteins had a higher level of phosphorylation in the HIV-1-primed cells. Furthermore, blockade of viral CD4 binding and fusion significantly reduced the negative effects DCs imposed on primed T cells. In conclusion, HIV-1 interaction with DCs modulated their functionality, causing them to trigger the activation of the P38MAPK/STAT3 pathway in T cells, which was responsible for the upregulation of inhibitory molecules. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00103
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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