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Expression and function of the atypical chemokine receptor CCRL1 in the thymus

Lucas, Beth (2015)
Ph.D. thesis, University of Birmingham.

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Abstract

Thymus colonisation and thymocyte positioning are mediated by interactions involving CCR7 and CCR9 and their respective ligands CCL19/CCL21 and CCL25. These chemokines also interact with the atypical receptor CCRL1, which is expressed in the thymus and has recently been reported to play an important role in normal abT-cell development. Our study has mapped CCRL1 expression within the adult and embryonic thymus, and shows that CCRL1 is expressed within the thymic cortex, at the subcapsular zone, and surrounding vessels at the corticomedullary junction. We have used flow cytometry to show CCRL1 expression predominantly by cortical thymic epithelial cells, but also by a small population of medullary thymic epithelial cells and by a subset of mesenchymal cells. We show, using CCRL1 deficient mice, that CCRL1 suppresses thymocyte progenitor entry into the thymus, and influences the intrathymic positioning of double negative thymocytes. Nevertheless, we have shown that CCRL1-/- mice have no major perturbations in T- cell populations at different stages of thymic differentiation and development. Overall, this study characterises the expression of CCRL1 in key thymic microenvironments, but argues against a major role for CCRL1 in normal thymus development and function.

Type of Work:Ph.D. thesis.
Supervisor(s):Rot, Antal and Anderson, Graham
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QP Physiology
QR Microbiology
RC Internal medicine
Institution:University of Birmingham
ID Code:5971
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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