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Altered antigen-presentation capacity of monocytes of Psoriatic arthritis patients

Friday 8 January 2016

Altered antigen-presentation capacity of monocytes of Psoriatic arthritis patients
Dr. Marianne Boes, Prof. dr. Tim Radstake
Tessa van Kempen, Laboratory of Translational Immunology (LTI), UMC Utrecht.

Psoriatic arthritis (PsA) is an ianflammatory disease and is clinically defined by swelling of the joints and enthesitis, combined with psoriasis in the skin. The immunopathogenesis of PsA, however, remains poorly understood. The contribution of MHC class I molecules may be significant in this disease, as supported by Genome-wide association studies (GWAS). Therefore, our hypothesis is that PsA is an antigen-driven CD8+ T-cell mediated disease. The presentation of endocytosed exogenous antigens via MHC class I molecules, known as cross-presentation, is important to activate CD8+ T-cells. This project concerns the investigation of endosomal processing pathways in monocytes from PsA and healthy donors for activation of CD8+ T-cells. SPPL2a is a late endosome-resident peptidase that processes type II transmembrane proteins including most notably the Class II MHC-associated chaperone protein invariant chain (Ii, CD74). Our preliminary data support that SPPL2a may be dysfunctional in PsA patient monocytes. Further, THP1 cells in which we depleted SPPL2a by use of CRISPR shows defective antigen cross-presentation to CD8+ T-cells. In this project, we would like to further clarify the role of SPPL2a in antigen-cross presentation and examine its possible role in cross-presentation capacity of PsA patient antigen-presenting cells.

Contact: Dr. Marianne Boes M.Boes@umcutrecht.nl