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Title

Regulation of Gut Commensal-Specific T Cell Differentiation by Dendritic Cell Subsets

ORCID

http://orcid.org/0000-0002-2036-6697

Date of Award

Spring 5-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Immunology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The mammalian gastrointestinal tract can harbor both beneficial commensal organisms important for host health, but also pathogenic organisms capable of intestinal damage. It is therefore important that the host immune system mounts appropriate responses to different intestinal organisms – promoting tolerance to some, controlling the colonization of others, and inducing sterilizing immunity in cases of noxious pathogens. Failure to induce tolerance to commensal organisms may underlie immune-mediated diseases such as human inflammatory bowel disease, while inappropriate tolerance to more harmful organisms has the potential to result in infection, inflammation, or even malabsorption. Adaptive immune responses to intestinal commensal organisms are driven by T cell subsets, the differentiation of which is governed by conventional dendritic cells (cDCs). This dissertation explores the roles of cDCs in the immune responses to two commensal organisms: colonic Helicobacter, and small intestinal Cryptosporidium. These studies revealed that appropriate T cell responses to Cryptosporidium, in contrast to Helicobacter, require a specialized cDC1 subset. Thus, we proposed a model in which Helicobacter-specific T cell tolerance induction by cDCs is ‘recessive’ as it requires all antigen presenting cDC subsets to facilitate peripheral regulatory T cell selection. In contrast, effector T cell differentiation to organisms such as Cryptosporidium by cDCs is ‘dominant’, in which a specific cDC subset drives Th1 cell development.

Language

English (en)

Chair and Committee

Chyi-Song Hsieh

Committee Members

Paul Allen, Kenneth Murphy, Thaddeus Stappenbeck, Wayne Yokoyama,

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