Defining the role of T cell dependent shaping of the microbiota to prevent dysbiosis and disease

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Title Defining the role of T cell dependent shaping of the microbiota to prevent dysbiosis and disease
Publication Type dissertation
School or College School of Medicine
Department Pathology
Author Petersen, Charisse N.
Date 2017
Description Harmful shifts within the microbiota, termed dysbiosis, are associated with an array of diseases that plague modern society. Dysbiosis may include loss of diversity, expansion of pathobionts, and reductions of beneficial microbes that are required for symbiosis with the host. While one or more of these alterations are identified in correlation to many disorders, the impetus for these dysfunctional communities has remained largely uncharacterized. One pathway that has likely evolved to maintain healthy microbiota populations is secretory immunoglobulin A (IgA), which shapes commensal communities and maintains tolerant hostmicrobe responses. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers along the gut, however, the molecular cues that govern T cell dependent IgA are largely unknown. This dissertation has uncovered a mechanism by which T cells use innate signaling through Toll-like receptors (TLRs) and Myeloid differentiation primary response gene 88 (MyD88) in order to detect shifts within the microbiota and direct IgA secretion. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to constrain bacterial communities, leading to dysbiosis. Animals lacking MyD88 signaling within T cells are more prone to developing increased colitis severity and metabolic syndrome, both of which can be treated by rescuing the dysbiotic microbiota to a healthy state. These findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota. This maintenance of healthy microbiota communities has widespread impacts on immune development and metabolism, highlighting the wide variety of physiological pathways that have evolved to depend on symbiotic host-microbiota interactions in order to promote health and prevent diseases.
Type Text
Publisher University of Utah
Subject Microbiology; Immunology
Dissertation Name Doctor of Philosophy
Language eng
Rights Management (c) Charisse N. Petersen
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6hx5s71
Setname ir_etd
ID 1404424
Reference URL https://collections.lib.utah.edu/ark:/87278/s6hx5s71
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