2026-09-22T14:12:41Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/97667 2023-07-11 col_2142_5131 col_2142_16338 com_2142_5130 com_2142_16337 com_2142_14793 com_2142_8903

text text Tapping, Richard I. Tapping, Richard I. Slauch, James M. Shisler, Joanna Blanke, Steven Hess, Nicholas James 2017-08-10T20:32:41Z 2017-08-10T20:32:41Z 2019-08-11T09:15:16Z 2017-03-28 2017-05 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. Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-05-01 The student, Nicholas Hess, accepted the attached license on 2017-03-24 at 14:53. The student, Nicholas Hess, submitted this Dissertation for approval on 2017-03-24 at 14:58. This Dissertation was approved for publication on 2017-03-28 at 13:41. DSpace SAF Submission Ingestion Package generated from Vireo submission #10616 on 2017-08-10 at 15:05:02 Made available in DSpace on 2017-08-10T20:32:41Z (GMT). No. of bitstreams: 3 HESS-DISSERTATION-2017.pdf: 2675516 bytes, checksum: d4e276e35a54d14f3b1b177ae6c5674a (MD5) LICENSE.txt: 4210 bytes, checksum: 8b79cc8a31e7fa9019eba38b12b2b978 (MD5) PROQUEST_LICENSE.txt: 4556 bytes, checksum: 9a5b0ec97982408408a4457bcb45921f (MD5) Previous issue date: 2017-03-28 Embargo set by: Colleen Fallaw for item 102720 Lift date: 2019-08-10T21:27:21Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system U of I Only Restriction Lifted for Item 102720 on 2019-08-11T09:15:16Z. application/pdf http://hdl.handle.net/2142/97667 en Copyright 2017 Nicholas Hess Toll-like receptor Immune suppression B cells Monocytes Characterizing the function of human toll-like receptor 10 Microbiology Microbiology University of Illinois at Urbana-Champaign Dissertation Ph.D.