1. Cytokine regulation of intestinal peristalsis
The neuroimmune interactions involve the actions of neurotransmitters, neuromodulators, and cytokines that carry signals, often bidirectionally, between enteric neurons and immune cells. Such dynamic interactions within the intestinal environment have profound consequences for gastrointestinal (GI) secretion and motility. Power propulsive motility is a recognizable component of an intestinal defense program and immunoneural communication activates the program. We will study how cytokines integrate in neural regulation on GI motility during intestinal homeostasis and inflammation.
2. Reciprocal regulation of colonic Treg cell (cTreg) and enteric neuron.
During central nervous system (CNS) inflammation, neurons are highly immune-regulatory governing T cell response. These modulations can be achieved via neuropeptides, which are received by neuropeptide receptors expressed on T cells. However, it is not clear whether similar interactions occur within GI compartment. Intestinal inflammation causes multiple changes in the intrinsic tissue motor circuits, including neuronal hyperexcitability and increased synaptic facilitation. It is known that enteric innervation contributes to the pathogenesis of intestinal bowel disease (IBD). On the other hand, cTreg cells are also reported to be critical modulators during intestinal inflammation. To establish the cooperative interactions between cTreg cells and the enteric neurons, both of which rapidly produce tissue-protective responses, will provide new therapeutic strategies for the treatment of IBD and irritable bowel syndrome (IBS).
3. Human ENS lineages for cell therapy and drug discovery in humanized colitis model.
In order to further develop therapeutic approaches to modify human neural and immune dysfunctions during intestinal inflammation, we will establish a humanized animal model which hosts either human T cells or the ENS or both.
