Arterial immune protein expression demonstrates the complexity of immune responses in Kawasaki disease arteritis.
Scott A CameronS M WhiteD ArrolloS T ShulmanA H RowleyPublished in: Clinical and experimental immunology (2017)
A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and in this study sought to determine protein expression of transcriptionally up-regulated immune genes in KD coronary arteries from the first 2 months after disease onset. We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly up-regulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR-7) and Z-DNA binding protein 1 (ZBP1). Immunohistochemistry and immunofluorescence studies were performed to evaluate protein expression and co-localization, respectively. AIF1 was expressed transmurally in KD arteritis and localized to macrophages and myeloid dendritic cells. CD74, which interacts with major histocompatibility complex (MHC) class II on antigen-presenting cells, localized to the intima-media. CD1c, a marker of myeloid dendritic cells, was expressed in a transmural pattern, as were IL-18 and CD20. ZBP1 and TLR-7 were up-regulated compared to controls, but less highly compared to the other proteins. These findings provide evidence of antigen presentation and interferon response in KD arteritis. In combination with prior studies demonstrating T lymphocyte activation, these results demonstrate the complexity of the KD arterial immune response.
Keyphrases
- dendritic cells
- immune response
- toll like receptor
- coronary artery
- coronary artery disease
- binding protein
- pulmonary artery
- regulatory t cells
- transcription factor
- inflammatory response
- nuclear factor
- genome wide
- case report
- gene expression
- induced apoptosis
- multiple sclerosis
- nk cells
- oxidative stress
- poor prognosis
- type diabetes
- young adults
- bone marrow
- cell proliferation
- left ventricular
- case control
- smoking cessation
- aortic stenosis
- genome wide identification
- single molecule
- cell cycle arrest
- kidney transplantation
- early life
- long non coding rna
- rna seq
- combination therapy
- atrial fibrillation