Abstract
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 γδT lymphocytes. It is known that iNKT cells regulate the development of Th17 lineage. Whether iNKT cells also regulate γδT lymphocytes differentiation is unknown. We found that iNKT cells play a protective role in ReA. BALB/c Jα18−/− 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 α-GalCer abrogated IL-17 response to Salmonella enterocolitis and prevented intestinal and joint tissue damage. Moreover, the anti-inflammatory effect of α-GalCer was related to a drop in the proportion of IL-17-producing γδT lymphocytes (IL17-γδTcells) 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-γδTcells.
Highlights
After infections of the gastrointestinal system a spondyloarthropathy which includes joint inflammation can arise
BALB/c Jα18−/− mice were kindly provided by Dr Masaru Taniguchi (Riken, Yokohama, Japan), wild type (WT) BALB/c mice were obtained from our vivarium; animals maintained in Abbreviations: Reactive arthritis (ReA), reactive arthritis; EC, enterocolitis; Inkt, Invariant natural killer T; TCR, T cell receptor; Jα18−/− KO, Jα18-knocked out; qPCR, quantitative Polymerase Chain Reaction; γδT, gamma delta T cells; IL17-γδTcells, IL-17 producers gamma delta T cells; α-GalCer, α-galactosylceramide; mesenteric lymph nodes (MLN), mesenteric lymph node
These cells have been suggested as the connection between both gut and joint inflammation during arthritis, as they are involved in IL-17 expression (Al-Mossawi et al, 2013). iNKT cells can exhibit proinflammatory and anti-inflammatory characteristics; depending on how they are activated, and the signals present in the resident environment (O’Keeffe et al, 2015)
Summary
After infections of the gastrointestinal system a spondyloarthropathy which includes joint inflammation can arise. This alteration is known as Reactive arthritis (ReA) (Townes, 2010). Earlier we have described an animal model for Salmonella enterocolitis in which soon after onset of infection, mice develop joint lesions (Noto Llana et al, 2009). During Salmonella enterocolitis, the increase in IL-17 expression is closely iNKT Cells Protect against Salmonellosis associated with both intestinal and joint damage (Noto Llana et al, 2012). When IL-17 expression is downregulated the intestinal and joint tissue injury is prevented (Noto Llana et al, 2013). The pathogenesis of ReA remains unclear, IL-17 generated in intestine and mesenteric lymph nodes plays a central role in the initial stages of this process (Noto Llana et al, 2012)
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