Fig. 1
From: Is air pollution a risk factor for rheumatoid arthritis?

Schematic representation of mechanisms putatively influencing rheumatoid arthritis through air pollution exposure. Four main mechanistic pathways are represented (blue, brown, red, and green arrows). Blue arrows: free reactive oxygen species released by fine/ultrafine particulate matter (PM) inhaled in the respiratory activate nuclear factor ƙappa B (NF-ƙB) that stimulates the production of tumor necrosis factor alpha (TNF-α), interleukin 1 (IL1) and interleukin 6 (IL6) by T helper lymphocytes type 1 (Th1). These cytokines stimulate resting monocytes to mature dendritic cells which then present autoantigens, co-stimulating self-reactive T lymphocytes that migrate to target tissues (preferentially synovial joints), and cause destruction of cells expressing autoantigens and thereby joint inflammation and erosion. Brown arrows: free reactive oxygen species cause chronic lung and systemic inflammation that enhance citrullination of arginine amino acid residues into citrullinated proteins/peptides. These citrullinated products induce anticyclic citrullinated protein/peptide antibodies (ACPAs) production that will later on lead to immune reaction through binding to cellular Fc receptors and complement activation, and finally cause joint inflammation and erosion. Red arrow: reactive oxygen species per se can worsen joint inflammation and erosion. Green arrows: Reduced ultraviolet B (UVB) radiation levels lead to decreased skin synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] which acts as an immunomodulator through vitamin D receptor (VDR) activation. Resultantly, immunomodulatory activities of 1,25(OH)2D3 represented by green doted arrows are not met, and RA can develop. IFN-γ interferon gamma; NK natural killer cells; and Treg T regulatory cells