Investigating the role of accessory cells in the thymic microenvironment for central tolerance and thymus regeneration

Cosway, Emilie Jade (2018). Investigating the role of accessory cells in the thymic microenvironment for central tolerance and thymus regeneration. University of Birmingham. Ph.D.

Preview

Cosway17PhD.pdf
PDF - Accepted Version
Download (36MB)

Abstract

Thymic microenvironments act to control T-cell development and selection. While thymic epithelial cells are key regulators of these processes, the thymus also contains multiple accessory cells that influence its function. Considering this, the major aim of this thesis is to examine the roles of dendritic cells and eosinophils in thymus biology. As regulation of thymic DC has previously been correlated to the thymic medulla we focused on the medullary regulator LTβR and generated cell type specific LTβR deficient mice. We found LTβR signalling regulates mTEC in a cell intrinsic manner, independent of thymic DC maintenance. Thymic DC alternatively require LTβR signalling on thymic mesenchyme for their regulation. Additionally, disruption of the medulla in Ltbr-/- mice was distinct from tolerance breakdown, which we instead found to correlate to reduced DC and impaired negative selection. Further we found the CCR7 ligand CCL21 was also required to control thymic DC, suggesting a link between these two pathways. Finally, dblGATA mice were used as a model of eosinophil deficiency and we identify a role for eosinophils in thymus recovery following sublethal irradiation damage. Collectively these findings shed new light on accessory cells during key aspects of thymus tolerance and regeneration.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):