Exposure to Dietary Nitrite Exacerbates Lupus in MRL/lpr Mice by Enhancing Integrin Alpha M.
Nitrite exposure worsens lupus by boosting immune cells and inflammatory markers, a discovery that could lead to new treatment strategies targeting the Itgam pathway.
This study used the MRL/lpr lupus mouse model to investigate the impact of dietary nitrite exposure on lupus pathogenesis. Nitrite intervention led to increases in disease-promoting immune cells (DN T cells, Tfh cells, plasma cells) and decreases in regulatory T cells. This was accompanied by elevated autoantibodies, inflammatory cytokines, and aggravated kidney damage. Transcriptome analysis revealed nitrite-induced changes in cell adhesion, osteoclast differentiation, and B cell receptor signaling pathways, with the Itgam (integrin alpha M) pathway emerging as a key mediator. Blocking Itgam attenuated the nitrite-induced lupus exacerbation, suggesting this pathway as a potential therapeutic target. These findings highlight the detrimental effects of excessive nitrite exposure on lupus and provide insights into the underlying mechanisms, which could inform the development of novel interventions.