Activation of iNKT Cells Prevents Salmonella-Enterocolitis and Salmonella-Induced Reactive Arthritis by Downregulating IL-17-Producing γδT Cells

Reactive arthritis (ReA) is an inflammatory condition of the joints that arises following an infection. Salmonella enterocolitis is one of the most common infections leading to ReA. Although the pathogenesis remains unclear, it is known that IL-17 plays a pivotal role in the development of ReA. IL-17-producers cells are mainly Th17, iNKT, and gamma delta T lymphocytes. It is known that iNKT cells regulate the development of Th17 lineage. Whether iNKT cells also regulate gamma delta T lymphocytes differentiation is unknown. We found that iNKT cells play a protective role in ReA. BALB/c J alpha 18(-/-) mice suffered a severe Salmonella enterocolitis, a 3.5-fold increase in IL-17 expression and aggravated inflammation of the synovial membrane. On the other hand, activation of iNKT cells with alpha-GalCer abrogated IL-17 response to Salmonella enterocolitis and prevented intestinal and joint tissue damage. Moreover, the anti-inflammatory effect of alpha-GalCer was related to a drop in the proportion of IL-17-producing gamma delta T lymphocytes (IL17-gamma delta Tcells) rather than to a decrease in Th17 cells. In summary, we here show that iNKT cells play a protective role against Salmonella-enterocolitis and Salmonella-induced ReA by downregulating IL17-gamma delta Tcells.