Why do epithelial cells have antigen processing machinery?

Overview

Epithelial Cells (ECs) constitute the border between the host immune system and an environment teeming with inhaled antigens. Work from us and others has highlighted that ECs have the ability to express the antigen processing and presentation machinery, Major Histocompatibility Complex class II (MHC II) that is important in initiating immune responses. MHC II expression and function on mucosal epithelial cells, is not well understood.

Whilst MHC II is expressed by ECs, and is altered with inflammation, there is a paucity of functional studies exploring the role of MHC II on ECs. A more complete understanding of the functional immunological consequences of EC MHC II antigen presentation will help us understand how immune tolerance is regulated and maintained in the mucosal tissue.

Aims:

• What is the role of MHC II class system on epithelial cells?
• How do endogenous cues regulate MHC II levels on epithelial cells?

References:

Wosen, J.E., et al, Epithelial MHC Class II Expression and Its Role in Antigen Presentation in the Gastrointestinal and Respiratory Tracts. Front Immunol, 2018. 9: p. 2144

Hasnain, S.Z., et al, The interplay between endoplasmic reticulum stress and inflammation. Immunol Cell Biol, 2012. 90(3): pp. 260-70

Haque, A., et al, A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications. Genome Med, 2017. 9(1): p. 75

Ramsey, K.A., et al, Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis. Am J Respir Crit Care Med, 2020. 201(6): pp. 661-670

Sonnenberg, G.F. and M.R. Hepworth, Functional interactions between innate lymphoid cells and adaptive immunity. Nat Rev Immunol, 2019. 19(10): pp. 599-613

Bonser, L.R., et al, Flow Cytometric Analysis and Purification of Airway Epithelial Cell Subsets. Am J Respir Cell Mol Biol, 2020.

Research activities

This project proposes to combine expertise in cellular stress and mucosal biology, lung biology, antigen presentation with new cross disciplinary approaches involving CITE-Seq, scRNA-Seq, in-vivo imaging and quantification of cell-cell interactions, spatial transcriptomics and expertise in cellular death pathways to conduct collaborative work to definitively dissect the role of MHC class II system on EC function.

You will conduct key primary cell culture experiments to determine whether epithelial cells have antigen presentation machinery that is functional.

You will also gain experience in the above-mentioned techniques, including:

• imaging
• cellular stress assays
• cell death assays
• CITE-Seq.

Outcomes

This project will span institutional and disciplinary boundaries with the aim of generating high-impact research that will address a fundamental knowledge gap in lung biology.

The new knowledge, technological advances and cross-disciplinary work generated through this project will provide a better understanding of the role of antigen presentation by epithelial cells.

With emerging data showing the impact of external environmental factors and a large number of drugs targeted to the respiratory and intestinal tract, the role of antigen presenting capacity of epithelial cells is a key piece of information that is missing in the field.

This project will generate a well refined transcriptomics atlas of the mucosal tissue (combination of CITE-Seq, Spatial Transcriptomics and CODEX) which will be made available publicly.

Skills and experience

You should have:

• an interest in mucosal immunology and/or cellular stress pathways
• a GPA 5.5 or above.

Scholarships

You may be eligible to apply for a research scholarship.

Explore our research scholarships

Keywords

• epithelial cells
• cytokines
• intestine
• mucosal immunology
• cellular stress
• antigen presentation
• respiratory tract

Contact

Contact the supervisor for more information