Identification of an interleukin (IL)-25–dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion

Abstract

Type 2 immunity, which involves coordinated regulation of innate and adaptive immune responses, can protect against helminth parasite infection, but may lead to allergy and asthma after inappropriate activation. We demonstrate that il25−/− mice display inefficient Nippostrongylus brasiliensis expulsion and delayed cytokine production by T helper 2 cells. We further establish a key role for interleukin (IL)-25 in regulating a novel population of IL-4–, IL-5–, IL-13–producing non–B/non–T (NBNT), c-kit+, FcɛR1− cells during helminth infection. A deficit in this population in il25−/− mice correlates with inefficient N. brasiliensis expulsion. In contrast, administration of recombinant IL-25 in vivo induces the appearance of NBNT, c-kit+, FcɛR1− cells and leads to rapid worm expulsion that is T and B cell independent, but type 2 cytokine dependent. We demonstrate that these IL-25–regulated cells appear rapidly in the draining lymph nodes, implicating them as a source of type 2 cytokines during initiation of worm expulsion.

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

“…**p < 0.01. compared to that of the DSS treated mice. (11,12). While an anti-inflammatory role for IL-25 was shown to be due to its ability in suppressing Th1 and Th17 responses (12), the promotion of host defense was shown to be via inhibition of expression of type 1 cytokines (11).…”

“…(11,12). While an anti-inflammatory role for IL-25 was shown to be due to its ability in suppressing Th1 and Th17 responses (12), the promotion of host defense was shown to be via inhibition of expression of type 1 cytokines (11). Yet, in a recent study, IL-25 was also reported to inhibit development and progress of inflammation in the brain and spinal cord (20).…”

“…Initially, treatment of mice with rIL-25 was shown to induce massive histological and pathological changes in the gastrointestinal (GI) tract (8). Lately, in parasitic intestinal infectious disease models, IL-25 was reported not only to limit production of pro-inflammatory cytokines but also to reduce chronic intestinal inflammation (11,12). In light of these earlier studies, we sought to evaluate the effect of rIL-25 on the development of acute DSS-induced experimental colitis.…”

Innate Lymphoid Cells in Type 2 Immune Responses

“…An initial description of a novel innate source of type 2 cytokines came from McKenzie, Fallon andcolleagues in 2006 (Fallon et al 2006). These researchers showed that infection of mice with the nematode parasite Nippostrongylus brasiliensis induced a non B/non T cell population that produced high levels of IL-4, IL-5 and IL-13 (Fallon et al 2006).…”

“…These researchers showed that infection of mice with the nematode parasite Nippostrongylus brasiliensis induced a non B/non T cell population that produced high levels of IL-4, IL-5 and IL-13 (Fallon et al 2006). Genetic deficiency in the IL-17 family cytokine IL-25 resulted in a failure to induce this novel population and was associated with inefficient clearance of the parasite.…”