Fig. 8: Model of role of HOIL1 in regulating type 2 inflammatory signaling.
From: HOIL1 regulates group 2 innate lymphoid cell numbers and type 2 inflammation in the small intestine
HOIL1 acts in a radiation-resistant cell type to suppress ILC2 proliferation and the production of IL-4, IL-5, and IL-13 in the presence of commensal microbes. HOIL1 may function to suppress the production of a positive regulatory factor (orange circles) upstream of IL-4, IL-5 and IL-13, or may be required for the negative regulation of ILC2 through a cell-extrinsic (pink circles) or cell-intrinsic mechanism, such as inhibition of IL17RB (IL25R) signaling. HOIL1 functions outside of the IL-13 – tuft cell – IL-25 feed-forward loop. In the absence of HOIL1, excessive IL-4, IL-5 and IL-13 can trigger chronic type 2 inflammation including goblet and tuft cell hyperplasia.
