Regulation of immune responses by tuft cells

Tuft cells are rare, secretory epithelial cells that generated scant immunological interest until contemporaneous reports in 2016 linked tuft cells with type 2 immunity in the small intestine. Tuft cells have the capacity to produce an unusual spectrum of biological effector molecules, including IL-25, eicosanoids implicated in allergy (such as cysteinyl leukotrienes and prostaglandin D2) and the neurotransmitter acetylcholine. In most cases, the extracellular signals controlling tuft cell effector function are unknown, but signal transduction is thought to proceed via canonical, G protein-coupled receptor-dependent pathways involving components of the signalling pathway used by type II taste bud cells to sense sweet, bitter and umami compounds. Tuft cells are ideally positioned as chemosensory sentinels that can detect and relay information from diverse luminal substances via what appear to be stereotyped outputs to initiate both positive and aversive responses through populations of immune and neuronal cells. Despite recent insights, numerous questions remain regarding tuft cell lineage, diversity and effector mechanisms and how tuft cells interface with the immunological niche in the tissues where they reside.