University of Illinois Urbana-Champaign

Characterizing the function of human toll-like receptor 10

Hess, Nicholas James

Content Files
HESS-DISSERTATION-2017.pdf

Permalink

https://hdl.handle.net/2142/97667

Description

Title
Characterizing the function of human toll-like receptor 10
Author(s)
Hess, Nicholas James
Issue Date
2017-03-28
Director of Research (if dissertation) or Advisor (if thesis)
Tapping, Richard I.
Doctoral Committee Chair(s)
Tapping, Richard I.
Committee Member(s)
  • Slauch, James M.
  • Shisler, Joanna
  • Blanke, Steven
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2017-08-10T20:32:41Z
Keyword(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.
Graduation Semester
2017-05
Type of Resource
text
Permalink
http://hdl.handle.net/2142/97667
Copyright and License Information
Copyright 2017 Nicholas Hess

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Microbiology