Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.822072
Title: Identifying novel molecules controlling CD4+ T cell-dendritic cell interactions
Author: Santos Bonilha, Caio
ISNI:       0000 0005 0286 8097
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2021
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Abstract:
CD4+ T cell interactions with dendritic cells (DC) are pivotal in adaptive immune responses and play an important role in both protective immunity (e.g. infection) and autoimmune diseases (e.g. rheumatoid arthritis). As such, there is increasing interest in discovering molecules that would promote/disrupt this interaction. Taking advantage of transcriptomic data generated in our lab using a murine model of inflammatory arthritis, we aimed to identify molecules that can control these interactions. We hypothesised that blockade of some of these molecules will disrupt these interactions, affecting T cell activation and/or migration of immune cells that promote pathology. This will not only further our basic understanding of disease processes but may also highlight potential therapeutic targets for human disease. The F11 receptor (F11R) gene, which encodes the junctional adhesion molecule-A (JAM-A), was identified in a gene list previously generated in the laboratory. F11R was upregulated in non-migratory leukocytes from inflamed joints in comparison to migratory immune cells. To investigate the role of JAM-A on CD4+ T cell activation, we employed in vitro and in vivo assays with cells from transgenic T cell receptor (TCR) mice (OTII). Treatment with an antagonistic anti-JAM-A monoclonal antibody (mAb) in vitro attenuated CD4+ T cell activation and proliferation and decreased T cell differentiation towards the Th1 subset in comparison with cells treated with its isotype control. In vivo, anti-JAM-A mAb treatment impaired CD4+ T cell proliferation in comparison with cells from mice treated with its isotype control. However, prophylactic treatment with anti-JAM- A mAb did not impact clinical disease in an acute, breach of self-tolerance model of arthritis. These findings are the first to describe a role for JAM-A during CD4+ T cell-DC interactions, but do not support JAM-A as a therapeutic target for rheumatoid arthritis (RA). Future work to evaluate the effects of treatment with JAM-A antagonists in late models of RA, in which autoimmune components may play a bigger role in clinical arthritis, or in models of other autoimmune diseases will further our understanding on JAM-A contribution to human disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.822072  DOI:
Keywords: QR180 Immunology
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