Investigating the immunoregulatory role of betaglycan

Barry, Robert John (2016). Investigating the immunoregulatory role of betaglycan. University of Birmingham. Ph.D.

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Abstract

Betaglycan, also known as TGFβRIII, is a component of the TGFβ receptor, being thought to act as a co-factor in signal transduction. It has proven roles in TGFβ-mediated embryogenesis and carcinogenesis, and facilitates signalling by activins and inhibins within the endocrine system. Despite the recognised importance of TGFβ in immunity, little is known about betaglycan in immune regulation.

In mice, absolute deficiency of any of the three isoforms of TGFβ, or any of the individual TGFβ receptor components results in embryonic or perinatal lethality, limiting the ability to study peripheral immune responses in these models. We developed a chimeric model in which betaglycan-deficient stem cells were transferred to immunodeficient hosts, allowing study of mature animals with betaglycan deletion restricted to T and B lymphocytes. We were thus able to investigate peripheral immune responses in vivo, and assess TGFβ signalling to T lymphocytes in vitro, in the presence and absence of betaglycan.

Betaglycan deficiency resulted in upregulated CD4+ and CD8+ T lymphocyte activation, with increased Th1 polarisation in peripheral lymphocyte compartments in both naïve and antigen-experienced animals. These observations confirm the involvement of betaglycan in T lymphocyte biology, providing the first evidence for its role in regulation of peripheral immune responses.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):