Regulatory T cell-Specific Wnt Secretion in Intestinal Homeostasis
Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Medzhitov, Ruslan
Abstract
As the longest section of the gastrointestinal tract, the small intestine is a major interface between the organism and its environment. It primarily serves to digest and absorb food, but because food is composed of nutrients and non-nutrients including pathogens and toxins, the small intestine must balance absorption with defense. These functions are finetuned by the intestinal immune system, which constantly evaluates food quality. Foods deemed “safe” result in immunological tolerance, or immune unresponsiveness, and are associated with the development of regulatory T cells (Tregs). Tregs are classically appreciated for their ability to suppress immune responses, and defects in Treg function have been widely associated with excessive immune activation and intestinal inflammation. In addition, several studies over the past decade have revealed a second important function of Tregs in tissue maintenance. This dissertation stems from an interest in exploring the dual functions of Tregs in tissue homeostasis and identifying novel mechanisms by which small intestine Tregs maintain normal gut function. I review small intestine digestion and absorption and regulatory T cell development and function in Chapter 1. In Chapter 2, I explore the consequences of mucosal Treg dysfunction on the small intestine and identify Treg mediators whose immune modulatory function may be specific to the small intestine. In Chapter 3, I identify the Wnt ligand Wnt4 as a candidate Treg mediator and characterize Wnt secretion as a novel Treg function that supports small intestine homeostasis. Chapter 4 examines the regulation of Wnt4. In Chapter 5, I provide a brief overview of environmental sensing mechanisms that help support the normal function of the gut. Chapter 6 concludes with a discussion of study implications and future directions.
Recommended Citation
Mitson-Salazar, Alyssa, "Regulatory T cell-Specific Wnt Secretion in Intestinal Homeostasis" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1391.
https://elischolar.library.yale.edu/gsas_dissertations/1391
