Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.798616
Title: The role of Fc receptor-like 6 in innate and adaptive immunity
Author: Patel, Yash
ISNI:       0000 0004 8507 987X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
Fc receptor-like 6 (FCRL6) is an immunoreceptor tyrosine-based inhibitory motif-bearing transmembrane receptor upregulated on human cytotoxic T and NK cells during chronic immune activation. It has been suggested to act as an inhibitory receptor by possibly interacting with human leukocyte antigen-DR (HLA-DR), but its function remains largely unknown. We initially investigated the role of FCRL6 in T cells using its murine counterpart. However, Fcrl6 expression was absent in developing, mature or activated mouse T cells. Therefore, we generated a human FCRL6 (hFCRL6) expressing transgenic mouse to investigate the function of this receptor. The expression of HLA-DR on antigen presenting cells resulted in reduced in vitro proliferation of hFCRL6+ CD4+ T cells. However, we were unable to recapitulate this inhibitory effect of the hFCRL6:HLA-DR axis in an in vivo environment. Further characterisation of mouse immune populations revealed Fcrl6 expression in natural killer (NK) and developing B cells. Analysis of Fcrl6-/- mice showed that the development of these cells as well as T cells and the splenic proportion of most major immune populations remained unaffected by FCRL6 deletion. We observed a reduction in the proportion of splenic macrophages and NK cells in Fcrl6-/- and NK conditional Fcrl6-/- mice, respectively. However, NK cell responses in a chronic retroviral infection model as well as a tumour model remained unaffected by FCRL6 deletion. Similarly, B cell antibody production in response to retroviral infection was also unaffected by FCRL6 deletion. Overall, data obtained here suggested that the mouse ortholog of FCRL6 might not possess the potential immunoregulatory capacity of its human counterpart and thus may have evolved to mediate non-immunoregulatory functions. Further studies will be required to define the role of mouse FCRL6 in NK cells and macrophages in addition to hFCRL6 in NK cells and T cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.798616  DOI: Not available
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