Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils

Abstract

23 24 25 2 26 ABSTRACT 27 28 Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, 29 eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue 30 and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including 31 TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several 32 genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. 33 In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil 34 responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation 35 by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis 36 and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our 37 results demonstrate that IL-33 can produce as potent or more eosinophil activation than IL-3, IL-5 and 38 eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to 39 consider for modulating eosinophil function. 40 41 42 111 Mg 2 + and washed with 3 times with HBSS. Cells, 1x10 4 eosinophils, were added to each well along with 112 the respective cytokines (1ng/ml final concentration). After 30 min at 37°C, wells were washed 3x with 113 HBSS to remove non adherent cells. 100ul of HBSS was added to sample wells and 100ul with 1x10 4114 eosinophils were added to untreated wells to provide "Total" eosinophils for comparison. Eosinophil

Rhinovirus Infection Promotes Eosinophilic Airway Inflammation after Prior Exposure to House Dust Mite Allergen

“…IL-33 is an epithelial cell-derived molecule, although it can also be made by macrophages. Recent experiments have suggested that IL-33 can be as potent as IL-5 and CCL11 in controlling eosinophil migration (30,31). We found increased IL-33 production in RV-infected HDM allergic mice, and the previously mentioned study demonstrated enhanced IL-33 expression in lung epithelial cells in cockroach allergen allergic mice and that blocking IL-33 partially reduced eosinophilia driven by RV (15), supporting a role for this cytokine.…”

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice

“…2a, b). In addition to acting through ILC2 and Th2 cells, IL-33 also acts directly on eosinophils, inducing their activation and expansion [63,64]. Therefore, its absence in IL-33 -/mice can explain the small number of eosinophils in the in ammatory in ltrates in the sixth week of infection (Fig.…”

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation, egg excretion, and the maintenance of egg-induced pathology in intestines of mice

“…Thus, it is understandable that the absence of IL-33 in IL-33 −/− mice at the early stage of the patent infection might have left them inactivated, leading to impaired type 2 immunity (58) as seen in the present study. In addition to acting through ILC2 and Th2 cells, IL-33 also acts directly on eosinophils, inducing their expansion and activation (59,60). Therefore, its absence in IL-33 −/− mice can explain the small number of eosinophils in the in ammatory in ltrates in the sixth week of infection (61).…”