Patel, Yash;
(2019)
The role of Fc receptor-like 6 in innate and adaptive immunity.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Thesis - Yash Patel.pdf Download (7MB) | Preview |
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The role of Fc receptor-like 6 in innate and adaptive immunity |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10086780 |
Archive Staff Only
 |
View Item |
