Devan, Jan. The role of T cells in mucosal immunity. 2022, Doctoral Thesis, University of Basel, Faculty of Science.
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Abstract
The mucosal immune system protects the human body on anatomic sites serving
to transport and exchange gases and nutrients with the outer environment. This makes
them exposed to pathogens more than any other tissue type, and to protect it, many
phenotypically and functionally different cell types contribute to the immune response
in the mucosal tissues. Maintaining the balance between an excessive and insufficient
immune response in such environmental conditions is key to homeostasis in the
mucosa. When disrupted, illnesses like Crohn’s disease (CD) or Eosinophilic
esophagitis (EoE) may develop.
My PhD thesis aimed to describe the changes in the phenotype and function of
immune cells associated with CD and EoE. Both of these diseases represent chronic
immune-mediated disorders with worldwide increasing incidence. T cells are thought
to play a key role in CD and EoE pathogenesis, and my research was therefore
primarily focused on their investigation.
I established an anti-CD45 mAbs-based barcoding approach to simultaneously
analyse hundreds of surface molecules expressed on cells isolated from intestinal
tissue samples. It led to identifying unique T cell populations in inflamed intestinal
tissue of CD patients and functional characterization of these T cells. In the EoE part,
I established a multicolour flow cytometry panel, which allowed the description of
changes in immune cell subsets composition, activation, and functional maturation
associated with EoE. In addition, I unraveled the possible existence of a vicious circle
in EoE where eosinophils present bacterial ligands to MAIT cells, which than produce
soluble factors stimulatory and chemotactic for eosinophils. Such a mechanism can
contribute to the perpetuation of chronic inflammation in EoE.
These results increase our understanding of the pathobiology of the studied diseases,
paving the design of novel successful targeted therapies in the future.
to transport and exchange gases and nutrients with the outer environment. This makes
them exposed to pathogens more than any other tissue type, and to protect it, many
phenotypically and functionally different cell types contribute to the immune response
in the mucosal tissues. Maintaining the balance between an excessive and insufficient
immune response in such environmental conditions is key to homeostasis in the
mucosa. When disrupted, illnesses like Crohn’s disease (CD) or Eosinophilic
esophagitis (EoE) may develop.
My PhD thesis aimed to describe the changes in the phenotype and function of
immune cells associated with CD and EoE. Both of these diseases represent chronic
immune-mediated disorders with worldwide increasing incidence. T cells are thought
to play a key role in CD and EoE pathogenesis, and my research was therefore
primarily focused on their investigation.
I established an anti-CD45 mAbs-based barcoding approach to simultaneously
analyse hundreds of surface molecules expressed on cells isolated from intestinal
tissue samples. It led to identifying unique T cell populations in inflamed intestinal
tissue of CD patients and functional characterization of these T cells. In the EoE part,
I established a multicolour flow cytometry panel, which allowed the description of
changes in immune cell subsets composition, activation, and functional maturation
associated with EoE. In addition, I unraveled the possible existence of a vicious circle
in EoE where eosinophils present bacterial ligands to MAIT cells, which than produce
soluble factors stimulatory and chemotactic for eosinophils. Such a mechanism can
contribute to the perpetuation of chronic inflammation in EoE.
These results increase our understanding of the pathobiology of the studied diseases,
paving the design of novel successful targeted therapies in the future.
Advisors: | De Libero , Gennaro |
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Committee Members: | Bumann, Dirk and Brand , Stephan |
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero) 05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann) |
UniBasel Contributors: | De Libero, Gennaro and Bumann, Dirk |
Item Type: | Thesis |
Thesis Subtype: | Doctoral Thesis |
Thesis no: | 15272 |
Thesis status: | Complete |
Number of Pages: | 132 |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 07 Feb 2024 05:30 |
Deposited On: | 06 Feb 2024 11:04 |
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