Investigate the regulatory effect of human IL-37 isoform a (IL-37a) on Toll-like receptor (TLR) response in vitro and in vivo

Ji, Yuan (2020) Investigate the regulatory effect of human IL-37 isoform a (IL-37a) on Toll-like receptor (TLR) response in vitro and in vivo. PhD thesis, University of Glasgow.

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Abstract

Background: Interleukin-37 is a newly discovered member of the IL-1 superfamily, consisting of 5 isoforms (IL-37a-e) due to different RNA splicing. Current studies are only focused on IL-37b isoform and demonstrate that IL-37b is an important immunosuppressive cytokine in TLR response in inflammatory diseases. However, the function and importance of other isoforms is still unknown. Here we investigate the function of IL-37 isoform a (IL-37a) which has a unique nuclear localisation sequence (NLS) and elastase cleavage sites in the protein N-terminal, while also containing the same receptor binding domain as IL-37b in the C-terminal.
Hypothesis: As IL-37a carries the same receptor-binding domain as IL-37b, the two isoforms may share the same receptor and signalling via similar pathway in the regulation of TLR function. However, the unique N-terminal domains may confer IL-37a additional function in nuclear translocation and gene regulation.
Aims:
1. To produce IL-37a and IL-37b recombinant proteins and transgenic mice. (Chapter 3).
2. To investigate the regulatory effect of IL-37a on TLR response in vitro and in a disease model (Chapter 4).
3. To explore the underlying molecular mechanism by which IL-37a and IL-37b differently affect TLR4 response in immune cells using transcriptomic analysis (Chapter 5).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Supported by funding from the China Scholarship Council.
Keywords: IL-37, TLR, Salmonella infection.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Immunology
Supervisor's Name: Xu, Dr. Damo and Wall, Dr. Donal
Date of Award: 2020
Depositing User: Mr. YUAN JI
Unique ID: glathesis:2020-80298
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 06 Apr 2020 15:36
Last Modified: 07 Apr 2020 14:02
Thesis DOI: 10.5525/gla.thesis.80298
URI: http://theses.gla.ac.uk/id/eprint/80298

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