Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Thymic epithelial cells (TECs) are indispensable for T cell development and maturation. Therefore, damages to the thymic epithelial cells are detrimental to thymic function and immune response. In young healthy individuals, TECs have a high regenerative potential and are capable of renewal from serious damage; however, the molecular mechanism of this recovery is unclear. A recent study has shown that IL-22-producing ILCs are present in the mouse thymus and can regenerate thymic epithelial cells following radiation induced injuries. However, it is unknown whether IL-22-producing cells are also found in the human thymus. Thus, the goal of this study is to identify IL-22 producing cells in the human thymus and to determine the mechanism by which IL-22 production is modulated. IL-22 is an effector cytokine that has been linked to promoting epithelial survival and proliferation within several secondary lymphoid tissues organs of mice and humans. To investigate the presence of IL-22-producing cells in the human thymus, we used flow cytometry and Reverse Transcriptase-PCR (RT-PCR) to analyze IL-22 expression in human pediatric thymocytes.

We reported that the highest percentage of IL-22-producing cells found in ex vivo thymocytes are the LIN-RORγt+IL-22+ cells and CD4+ RORγt+IL-22+ T cell subsets. We also reported that the production of IL-22 by the LIN-RORγt+IL-22+ cells and the CD4+ RORγt+IL-22+ T cells are not solely modulated by TECs. Furthermore, although the frequency of circulating RORγt-expressing ILC3-derived IL-22 increased following

PBMC co-cultured with TECs, we could not rule out whether this effect is likely due to allogenic T cell response and/or cytokines produced by the activated allogenic T cells. Since so much is still unknown about IL-22 biology, particularly in the human thymus, the results from study contribute to our current understanding of the biology of IL-22 with the expectation that the new findings provide opportunities towards elucidating the mechanism of thymus regeneration, repair and maintenance.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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