Congratulations!

Our findings reveal a protective role for GSDMC in intestinal epithelial cells during helminth infection- and expand the function of gasdermins beyond classical roles in pyroptosis and cytokine release

Using a clever approach (Yi-Nan), we showed that inserting a single amino acid within the lipid binding motif (to mimic pyroptotic gasdermins) enhances GSDMC oligomerization and increases its ability to induce cell death

Mechanistically, cleaved GSDMC doesn’t localize to the plasma membrane as typical gasdermins do (eg GSDMD) Rather, GSDMC targets Rab7+ vesicles (late endosomes) leading to lipid droplet accumulation, which in turn promotes goblet cell hyperplasia and type 2 immune responses

Similar to findings by Drs Hai-Bin Ruan and Xiaoyu Hu, we observed that GSDMC activation does NOT drive epithelial cell (IEC) death. Instead, we found that intestinal GSDMC is not cleaved by caspases, but DIRECTLY by the cysteine protease Cathepsin S generating a functional GSDMC-Nter

GSDMC is barely expressed in the intestine but is induced 100-fold and cleaved (activated) in response to type-2 triggers like helminth infection or colonization by the commensal protist Tritrichomonas.

Big thank you to our amazing collaborators @meisellab.bsky.social @jmoltke.bsky.social and Suhong Xu #GSMC #Helminth #Tritrichomonas #type-2-immunity