Submission Title

Interferon-gamma Antagonizes Type 2 Immune Drive Tuft Cell Hyperplasia

Presenter Information

Rachel Noyes, Gonzaga University

Session Number

RS15

Location

Weyerhaeuser 303

Abstract Number

RS15-b

Abstract

Generation of a type 2 immune response, which underlies anti-helminth immunity and the pathogenesis of allergies, requires the secretion of the endogenous cytokines interleukin(IL)-4 and IL-13. Interferon(IFN)-γ, by contrast, promotes a type 1 immune response. The intestinal epithelium consists of a stem cell compartment and a variety of differentiated cell types, including tuft and goblet cells. Clearance of helminths from the intestine requires epithelial remodeling that leads to tuft and goblet cell hyperplasia, which result from IL-4/13 signals that bias progenitor fates toward these lineages. Here we demonstrate the ability of interferon gamma to suppress IL-4/13 induced tuft cell hyperplasia ex vivo using mouse small intestine epithelial organoids. These data suggest a previously unknown ability of IFN-γ to directly impact the differentiation of intestinal epithelial stem cells. This provides new insight into the mechanisms by which IFN-γ antagonizes type 2 responses that protect against parasitic helminthes and underlie allergic asthma.

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Apr 23rd, 3:15 PM Apr 23rd, 4:45 PM

Interferon-gamma Antagonizes Type 2 Immune Drive Tuft Cell Hyperplasia

Weyerhaeuser 303

Generation of a type 2 immune response, which underlies anti-helminth immunity and the pathogenesis of allergies, requires the secretion of the endogenous cytokines interleukin(IL)-4 and IL-13. Interferon(IFN)-γ, by contrast, promotes a type 1 immune response. The intestinal epithelium consists of a stem cell compartment and a variety of differentiated cell types, including tuft and goblet cells. Clearance of helminths from the intestine requires epithelial remodeling that leads to tuft and goblet cell hyperplasia, which result from IL-4/13 signals that bias progenitor fates toward these lineages. Here we demonstrate the ability of interferon gamma to suppress IL-4/13 induced tuft cell hyperplasia ex vivo using mouse small intestine epithelial organoids. These data suggest a previously unknown ability of IFN-γ to directly impact the differentiation of intestinal epithelial stem cells. This provides new insight into the mechanisms by which IFN-γ antagonizes type 2 responses that protect against parasitic helminthes and underlie allergic asthma.