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Title:Characterizing the function of human toll-like receptor 10
Author(s):Hess, Nicholas James
Director of Research:Tapping, Richard I.
Doctoral Committee Chair(s):Tapping, Richard I.
Doctoral Committee Member(s):Slauch, James; Shisler, Joanna; Blanke, Steven
Department / Program:Microbiology
Discipline:Microbiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Toll-like receptor
Immune suppression
B cells
Monocytes
Abstract:Toll-like Receptors (TLRs) are important constituents of the immune response, capable of both protecting the host from danger and inciting harm from within. In this Thesis, I present evidence that the last human orphan toll-like receptor, TLR10, has a unique function that differs from its other family members in that TLR10 is capable of suppressing inflammatory responses. I will describe the relationship between pattern-recognition receptors (PRRs) and the maintenance and induction of chronic inflammation to underscore the importance of TLR10’s novel suppressive function. I will then present multiple different lines of evidence that TLR10 is a suppressor of inflammatory responses. Our experimental approaches included transfected cell lines, antibody-mediated engagement on primary human leukocytes and the development of two different transgenic mouse lines. Taken together, our data show that TLR10 is capable of suppressing both TLR-dependent and –independent stimulatory signals within both monocytes and B cells as evidenced by inhibitory effects on phosphorylation of signaling proteins, the transcriptome, secretion of cytokines, proliferation, differentiation, cellular co-stimulation and antibody generation. The research findings suggests that TLR10 could be a useful therapeutic target in the resolution of chronic inflammatory conditions, especially autoimmune diseases that are driven by overactive B cells. In summary, this Thesis outlines the novel understanding that as a previously uncharacterized TLR, TLR10 can function as a broad immune suppressor on primary human leukocytes.
Issue Date:2017-03-28
Type:Thesis
URI:http://hdl.handle.net/2142/97667
Rights Information:Copyright 2017 Nicholas Hess
Date Available in IDEALS:2017-08-10
Date Deposited:2017-05


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