Identification of antigen-presenting cell-T cell interactions driving immune responses to food.

The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4 T cells and inducing their differentiation into regulatory (pTreg) or inflammatory (Th) subsets. We used a proximity labeling method (LIPSTIC) to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions and understand cellular mechanisms by which tolerance to food is induced and can be disrupted by infection.

Gut bacteria-derived succinate induces enteric nervous system regeneration.

Enteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion . Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders . However, the signals and underlying mechanisms of this microbiota-neuron communication are unknown.

Intestinal tuft cell immune privilege enables norovirus persistence.

The persistent murine norovirus strain MNV is a model for human norovirus and enteric viral persistence. MNV causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNV induces functional MNV-specific CD8 T cells, these lymphocytes fail to clear infection.

Universal recording of immune cell interactions in vivo.

Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function. To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts), an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4 T helper cells and antigen-presenting cells, however.

Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression.

Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation.