CXCL4 is a chemokine released by activated platelets and immune cells. Our group and others have found increased levels of CXCL4 in circulation and in skin of patients with systemic sclerosis (SSc).
Changes in frequency and activation of platelets and immune cells are implicated in aberrant inflammatory and fibrotic responses associated with the pathology of SSc.
In this thesis we investigated whether exposure to CXCL4 potentiates pro-inflammatory and pro-fibrotic responses by moDCs. Additionally we explored the underlying molecular mechanisms implicated in the reprogramming of moDC phenotype and function by CXCL4.
We found that exposure to CXCL4 drives to a semi-mature phenotype and morphology of moDCs, amplifies aberrant TLR-mediated responses and potentiates the activation of autologous and antigen specific T-cell responses.
CXCL4-mediated immunogenic responses are regulated at the transcriptional, post-transcriptional and epigenetic level.