ABSTRACT WATCH: Interleukin-4 directly promotes intestinal mast cells expansion in the context of food allergy

cropped-wp-1466319340412.jpgABSTRACT WATCH: Interleukin-4 directly promotes intestinal mast cells expansion in the context of food allergy

Oliver Burton, Alanna Darling, Joseph Zhou, Magali Noval-Rivas, Tatiana Jones, Michael Gurish, Talal Chatila and Hans Oettgen

Interleukin-4 is a pivotal cytokine in the development of allergic disorders. Mast cells are key effectors of food allergen-driven anaphylaxis, and IL-4 has been implicated in their function. More recently, however, we and others have shown that IL-4 has a mix of inhibitory and stimulatory effects on bone marrow-derived mast cells. We therefore sought to clarify the direct effects of IL-4 on intestinal mast cell function and growth. In this study, we demonstrate that IL-4 drives a marked intestinal mastocytosis in mice. Similar effects were observed in animals expressing Il4rαF709, an activating variant of the IL-4 receptor α-chain that confers susceptibility to food allergen-driven anaphylaxis. Il4rαF709 mice show heightened sensitivity to IgE-mediated anaphylaxis without increased sensitivity to mast cell mediators. Exposure to IL-4 upregulates anti-apoptotic Bcl proteins in intestinal mast cells, leading to enhanced survival and proliferation via STAT6. These effects are intensified by the Il4rαF709 signaling variant. Mixed bone marrow chimera experiments demonstrate that Il4rαF709 mast cells hold a substantial competitive advantage over wild-type cells in populating the intestine in response to food allergen stimulation. IL-4Rα-deficient mast cells do not effectively expand, establishing a cell-intrinsic effect of IL-4 in intestinal mast cell homeostasis. Our results demonstrate that IL-4-signaling is a key determinant of mast cell expansion in food allergy.

Tinggalkan Balasan

Isikan data di bawah atau klik salah satu ikon untuk log in:

Logo WordPress.com

You are commenting using your WordPress.com account. Logout /  Ubah )

Foto Google

You are commenting using your Google account. Logout /  Ubah )

Gambar Twitter

You are commenting using your Twitter account. Logout /  Ubah )

Foto Facebook

You are commenting using your Facebook account. Logout /  Ubah )

Connecting to %s