IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger

Abstract

IL-17 is a cytokine implicated in the regulation of inflammation. We investigated the role of this cytokine in neutrophil recruitment using a model of LPS-induced lung inflammation in mice. In the bronchoalveolar lavage, LPS induced a first influx of neutrophils peaking at day 1, followed by a second wave, peaking at day 2. IL-17 levels were increased during the late phase neutrophilia (day 2), and this was concomitant with an increased number of T cells and macrophages, together with an increase of KC and macrophage-inflammatory protein-2 levels in the lung tissue. Intranasal treatment with a neutralizing murine anti-IL-17 Ab inhibited the late phase neutrophilia. In the bronchoalveolar lavage cells, IL-17 mRNA was detected at days 1, 2, and 3 postchallenge, with a strong expression at day 2. This expression was associated with CD4+ and CD8+ cells, but also with neutrophils. When challenged with LPS, despite the absence of T cells, SCID mice also developed a neutrophilic response associated with IL-17 production. In BALB/c mice, IL-15 mRNA, associated mainly with neutrophils, was evidenced 1 day after LPS challenge. In vitro, IL-15 was able to induce IL-17 release from purified spleen CD4+ cells, but not spleen CD8+ or airway neutrophils. We have shown that IL-17, produced mainly by CD4+ cells, but also by neutrophils, plays a role in the mobilization of lung neutrophils following bacterial challenge. In addition, our results suggest that IL-15 could represent a physiological trigger that leads to IL-17 production following bacterial infection.

IL‐15 exacerbates collagen‐induced arthritis with an enhanced CD4+ T cell response to produce IL‐17

“…It was also shown that IL-15 induced IL-17 production from splenic CD4 + cells in BALB/c mice [32]. Thus, IL-17 may also be involved in the IL-15-mediated pathogenesis of chronic arthritis in both humans and mice.…”

“…3B). These results suggest that CD4 + T cells expressing functional IL-23R and producing IL-17 were increased in IL-15 Tg mice at the chronic phase of CIA.IL-15 has been shown to be a potent enhancer of IL-17 production from CD4 + T cells in vitro [31,32]. The results of these studies and our results raise the possibility that IL-15 has an activity to enhance Agspecific IL-17 production in addition to a bystander production of IL-17 in response to IL-23 as shown above.…”

Induction, function and regulation of IL‐17‐producing T cells

“…Furthermore, although T cells are a major source of IL-17, they are not the only source of this cytokine. Neutrophils, as well as T cells, have been shown to produce IL-17 in response to IL-15 [23]. In addition, the precise subpopulation(s) of T cells that secrete IL-17 remain unclear.…”

Ciona intestinalis interleukin 17-like genes expression is upregulated by LPS challenge

“…The IL-17A and F are produced by a class of effectors αβ T cells (Th17 and CD8+ cells), NK cells and neutrophils (Ciric et al, 2009;Michel et al, 2008;Weaver et al, 2007). They induce the expression of numerous inflammatory mediators including IL-8, CXC chemokines, granulocyte-colony stimulating factor and prostaglandin E2 (Ferretti et al, 2003;Jones and Chan, 2002;Ruddy et al, 2004). IL-17 displays proinflammatory properties, like those of tumour necrosis factor α (TNFα), in its capacity to induce other inflammatory effectors (Benderdour et al, 2002;Gaffen, 2004), and synergizes with other cytokines at the center of the inflammatory network (Gaffen, 2004) to activate the nuclear factor κB (Hata et al, 2002).…”