Cellular and molecular perspectives in rheumatoid arthritis.
Douglas James VealeCarl OrrUrsula FearonPublished in: Seminars in immunopathology (2017)
Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA. Abnormal cellular metabolism and mitochondrial dysfunction thus ensue and, in turn, through the increased production of reactive oxygen species actively induce inflammation. Key pro-inflammatory cytokines, chemokines and growth factors and their signalling pathways, including nuclear factor κB, Janus kinase-signal transducer, are highly activated when immune cells are exposed to hypoxia in the inflamed rheumatoid joint show adaptive survival reactions by activating. This review attempts to highlight those aberrations in the innate and adaptive immune systems including the role of genetic and environmental factors, autoantibodies, cellular alterations, signalling pathways and metabolism that are implicated in the pathogenesis of RA and may therefore provide an opportunity for therapeutic intervention.
Keyphrases
- rheumatoid arthritis
- disease activity
- nuclear factor
- early stage
- rheumatoid arthritis patients
- systemic lupus erythematosus
- reactive oxygen species
- ankylosing spondylitis
- interstitial lung disease
- toll like receptor
- induced apoptosis
- immune response
- randomized controlled trial
- oxidative stress
- signaling pathway
- peripheral blood
- stem cells
- copy number
- endoplasmic reticulum stress
- dendritic cells
- endothelial cells
- tyrosine kinase
- genome wide
- sensitive detection
- systemic sclerosis
- lymph node
- diabetic retinopathy
- squamous cell carcinoma
- vascular endothelial growth factor
- fluorescent probe
- protein kinase
- free survival
- small molecule
- amino acid
- cell proliferation
- neoadjuvant chemotherapy
- radiation therapy
- pi k akt
- rectal cancer