Characterizing the function of human toll-like receptor 10

Hess, Nicholas James

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

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

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

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

Copyright and License Information

Copyright 2017 Nicholas Hess

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