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Cross Talk between ...
Cross Talk between P38MAPK and STAT3 Regulates Expression of Negative Costimulatory Molecules and Transcriptional Repressors in HIV-1 Primed T cells
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- Che, Karlhans Fru (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Shankar, Esaki M (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Sundaram, Muthu (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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- Zandi, Sasan (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,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)
- Moores Cancer Center, University of California San Diego, La Jolla, USA
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- Bhardwa, N (author)
- New York University School of Medicine, New York, NY, USA
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- Lifson, Jeffrey D (author)
- AIDS and Cancer Virus Program SAIC Frederick Inc., National Cancer Institute at Frederick, Maryland, USA
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- Larsson, Marie (author)
- Linköpings universitet,Molekylär virologi,Hälsouniversitetet
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- HIV-1 infection enhances the expression of negative costimulatory molecules on T cellsleading to T cell impairment. The signaling pathway underlying the regulation ofinhibitory molecules and the subsequent onset of T cell impairment remains to beinvestigated. Herein, we showed that the T cells activated by HIV-pulsed dendritic cells(DCs) upregulated CTLA-4, TRAIL, LAG-3, TIM-3, and CD160 and suppressionassociated transcription factors BLIMP-1, DTX1, and FOXP3, leading to T cellsuppression. The induction of suppressor T cells was regulated by the signal transducerand activator of transcription 3 (STAT3) molecules as blockade of this pathwaysignificantly down regulates the expression of inhibitory molecules. The cytokines IL-6and IL-10 were not responsible for STAT3 activation as their neutralization could neitherrecover T cell proliferation nor decrease the expression of negative costimulatorymolecules. Contrarily, we demonstrated that the intracytoplasmic cross-talk of P38Mitogen-Activated Protein Kinase (MAPK) with STAT3 was responsible as blockade ofthe P38MAPK significantly impaired negative costimulatory molecular expression andthe subsequent recovery of T cell proliferation. Notably, the blockade of viral access toDC cytosol, via CD4 binding and fusion, significantly reduced the negative effects DCsimposed on the primed T cells. In conclusion, viral access to cytosol modulated theDCs- T cell priming to induce T cells with upreguled expression of negativecostimulatory molecules in a P38MAPK/STAT3 pathway dependent fashion
Keyword
- BLIMP-1; dendritic cells; HIV-1; LAG-3; P38MAPK
- STAT3; T cells
- MEDICINE
- MEDICIN
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Che, Karlhans Fr ...
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Shankar, Esaki M
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Sundaram, Muthu
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Zandi, Sasan
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Sigvardsson, Mik ...
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Hinkula, Jorma
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Messmer, Davorka
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Bhardwa, N
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Lifson, Jeffrey ...
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Larsson, Marie
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- By the university
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Linköping University