Role of Wnt5A Signaling in Antigen Processing and Presentation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Role of Wnt5A Signaling in Antigen Processing and Presentation
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| Creator |
Sarraf, Tresa Rani
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
The adaptive immune system relies on the efficient processing of exogenous antigens and the cross-presentation of antigen to T cells. Dendritic cells are potent antigen-presenting cells, which have the ability to cross-present antigens and promote the generation of antigen-specific CD8 T cell response. Yet several questions remain unresolved in dendritic cell-mediated antigen cross-presentation. One of the very important questions in this field is how dendritic cells regulate the supply of exogenous antigens to the conventional exogenous pathways or cross-presentation pathways. The host factors that decide and modulate the cross-presentation of exogenous antigens are still unknown. In this study, I demonstrated that host protein Wnt5A, as an immune modulator, promotes cross-presentation in both in-vitro and in-vivo systems. Using mouse bone marrow-derived dendritic cells (BMDC) as antigen-presenting cells and ovalbumin (OVA/DQ-OVA) as a model antigen, I demonstrated that recombinant Wnt5A treatment promotes DQ-OVA processing in BMDC in combination with actin dynamics. Recombinant Wnt5A facilitated DQ-OVA processing depends on proteasome and is compromised by proteasome inhibitor MG132. Mechanistically I demonstrated that Wnt5A depletion leads to reduced DQ-OVA processing and is accompanied by the lower association of actin and proteasome 11S subunit with processed DQ-OVA. Further, I showed that the Wnt5A-actin-proteasome axis directs the antigen cross-presentation and subsequent activation of CD8 T cells. Reduction of Wnt5A results in compromised CD8 T cell activation. Using Wnt5A wild type and heterozygous mice I demonstrated that reduced levels of Wnt5A protein in heterozygous mice led to impaired CD8 T cell activation in presence of ovalbumin. Overall my results proved that Wnt5A signaling is the prerequisite for antigen processing and cross-presentation, thus unveiling a new field in the therapeutic vaccine.
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| Date |
2022
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2862/1/Thesis_for_evaluation.pdf
Sarraf, Tresa Rani (2022) Role of Wnt5A Signaling in Antigen Processing and Presentation. PhD thesis, UNIVERSITY OF CALCUTTA. |
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| Relation |
http://www.eprints.iicb.res.in/2862/
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