Investigating the functional biology of IL-25 during helminth infection (38.6)

Abstract

Abstract Recent studies have demonstrated key functions of interleukin (IL) -25 in TH2 cytokine-mediated host protective immunity and exacerbation of allergic airway inflammation, however the cell lineages targeted by IL-25 to elicit such responses remains unclear. We show that IL-25 acts through an innate cell mechanism to drive TH2 cytokine responses. Utilizing IL-4/eGFP reporter mice that express green fluorescent protein (GFP) under the IL-4 loci, we demonstrated that IL-25 specifically induced a c-kit+ cell population in the mesenteric lymph nodes. This population was also present in the Peyer's patches, cecal patch, and peritoneum of treated mice. Despite displaying a cell morphology similar to classical mast cells, the IL-25-induced c-kit+ cell population lacked expression of FcεR1 and surface bound IgE. Additionally, IL-25 elicited a TH2 cytokine response and induced this c-kit+ cell population independently of IL-3 and SCF signaling, pathways known to regulate mast cell development. Furthermore, we demonstrated that in mice deficient in the receptor for IL-25 or IL-17A, IL-17Rb and IL-17Ra respectively, the IL-25-mediated induction of this c-kit+ population was lost. Thus, these data suggest that IL-25 acts through a mast-cell independent mechanism to promote TH2 cytokine responses, which is dependent on both IL-17Ra and IL-17Rb.