Figure 2.

Cytothripsis promotes allergic type cytokine production in DOCK8 deficiency. As shown in [34], loss of Dock8 in mice results in cytothripsis of mononuclear phagocytes as they travel through certain tissues. The cell death activates caspases, which process pro-IL-1β into its mature form that is released from the dying cell. IL-1β stimulates CD4⁺ T cells to increase their production of GM-CSF, which in turn feeds back to increase pro-IL-1β expression for amplification of cytokine responses. Caspases, IL-1β, and GM-CSF are required for the resulting increased production of IL-4, IL-5, and IL-13 to predispose to allergy. Created with Biorender.com.