Periodic Reporting for period 1 - TIPPDECRA (Tolerogenic immunotherapy with peptide-pulsed dendritic cells in rheumatoid arthritis)
Okres sprawozdawczy: 2016-05-05 do 2018-05-04
The objectives of this research were:
1) to select small, relevant heat shock protein components (called HSP-peptides) that can be loaded onto tolDC
2) to show that these HSP-peptide-loaded tolDC can tolerise immune cells from RA patients
3) to study weather HSP-loaded tolDC are capable of ameliorating disease severity in a mouse model of rheumatoid arthritis
• We found 4 different HSP-peptides that could be recognised by immune cells – T cells – from blood in 80% of RA patients and healthy donors. These immune cell responses were of a pro-inflammatory nature, meaning that they can potentially cause harm after binding the HSP-peptide.
• We added tolDC to these cultures to determine whether tolDC could make these same T cells harmless – and make them instead produce immune mediators that can ‘turn off’ other pro-inflammatory – i.e. harmful – immune cells. Indeed, in this research we showed that tolDC can activate these HSP-recognising T cells in such a way that they now produce anti-inflammatory mediators that can potentially suppress harmful immune cells in the arthritic joints.
• Interestingly, when studying the other immune cells also present in the culture, we found that the tolDC also directly suppressed other harmful immune cells by secreting specific anti-inflammatory mediators named TGFβ. The tolDC could severely inhibit these cells from proliferating/multiplying and thereby potentially reduce destruction in the joint.
• We then investigated whether the HSP-peptide-loaded tolDC could suppress disease in a mouse model of arthritis. Indeed, we found that tolDC injected prior to disease induction could significantly suppress disease as compared to mice that did not receive tolDC. However, more work is needed to understand how tolDC affect the immune response in vivo.