Characterizing the function of human toll-like receptor 10

Toll-like receptor;Immune suppression;B cells;Monocytes

Hess, Nicholas James

关键词: Toll-like receptor;    Immune suppression;    B cells;    Monocytes;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/97667/HESS-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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.