Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.

Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

Intestinal tuft cells: Sentinels, what else?

The intestinal epithelium plays crucial roles in maintaining gut homeostasis. A key function consists in constituting a physical and chemical barrier between self and non-self-compartments, and, based on its crosstalk with the luminal environment, in controlling activation of the host immune system. Tuft cells are a unique epithelial cell lineage, the function of which remained a mystery even 50 years after their initial discovery. The first function of intestinal tuft cells was recently described, with a central role in initiating type 2 immune responses following infection with helminth parasites. Since then, tuft cells have emerged as sentinel cells recognizing a variety of luminal cues, mediating the host-microorganisms crosstalk with additional pathogens, including viruses and bacteria. Although it can be anticipated that more functions will be discovered for tuft cells in the future, recent discoveries already propelled them at the forefront of gut mucosal homeostasis regulation, with important potential impact in gut physiopathology. This review focuses on intestinal tuft cells, from their initial description to the current understanding of their functions, and their potential impact in diseases.

Involvement of Bcl-xL in Neuronal Function and Development.

The B-cell lymphoma (Bcl-2) family of proteins are mainly known for their role in the regulation of apoptosis by preventing pore formation at the mitochondrial outer membrane and subsequent caspase activation. However, Bcl-2 proteins also have non-canonical functions, independent of apoptosis. Indeed, the cell death machinery, including Bcl-2 homologs, was reported to be essential for the central nervous system (CNS), notably with respect to synaptic transmission and axon pruning. Here we focused on Bcl-xL, a close Bcl-2 homolog, which plays a major role in neuronal development, as bclx knock out mice prematurely die at embryonic day 13.5, showing massive apoptosis in the CNS. In addition, we present evidence that Bcl-xL fosters ATP generation by the mitochondria to fuel high energy needs by neurons, and its contribution to synaptic transmission. We discuss how Bcl-xL might control local and transient activation of caspases in neurons without causing cell death. Consistently, Bcl-xL may contribute to morphological changes, such as sprouting and retractation of axon branches, in the context of CNS plasticity. Regarding degenerative diseases and aging, a better understanding of the numerous roles of the cell death machinery in neurons may have future clinical implications.