First identified in 1956, intestinal tuft cells are a rare cell type, described by their discoverers as “peculiar cells.” New studies reveal that these intriguing cells contain a unique cytoskeleton that could unlock new insights into human health.
Tuft cells were termed peculiar because of the long finger-like protrusions that extend from their apex, creating a “tuft” that projects into the lumen of the gut. These structures are supported by actin, a molecule important for a cell’s structural integrity. Although tuft cells were discovered decades ago, their function has only recently been investigated. Tuft cells can sense the presence of harmful microorganisms, like parasitic worms, and generate an immune response that removes them from the intestine. Additionally, tuft cells have roles in restoring the intestine from chronic inflammation in ulcerative colitis and Crohn’s disease by secreting anti-inflammatory molecules.
Although tuft cells are important in parasitic worm clearance and regulating intestinal inflammation, not much is known about how their tuft, or cytoskeleton, supports their necessary functions.
Graduate student Jennifer Silverman and her mentor Matthew Tyska, PhD, Cornelius Vanderbilt Professor of Cell and Developmental Biology, utilized advanced imaging techniques to detail the microscopic structure of intestinal tuft cells, highlighting their unique organization of actin. Importantly, using single-cell sequencing data from the laboratory of Ken Lau, PhD, professor of Cell and Developmental Biology, they identified tuft cell-specific actin binding proteins that could support both the tuft cytoskeleton and cellular transport of molecules along this structure. The researchers suggest these tuft cell-specific proteins can aid in the sensing of danger molecules and the transport of tuft cell-derived anti-inflammatory molecules.
The investigators note that identifying specific structural tuft cell proteins can help us understand how our gut protects us from infection and chronic inflammation. Their discovery can potentially be harnessed to battle intestinal inflammatory diseases, highlighting the significance of tuft cells in addressing this growing health challenge.
The study was published Oct.1 in the Journal of Cell Biology. Other author contributors include Evan Krystofiak, PhD, Leah Caplan and Ken Lau, PhD. This work was supported by the National Institutes of Health (F31DK141157, R01DK103831, R01DK095811, R01DK125546, R01DK111949).
