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Intestinal immune system 1

 

T cells

T Cell Biology

Our studies have shown that effector T cells can contribute to pathology within the gut while regulatory T cells play an important role in maintaining and re-establishing homeostasis. Our lab is interested in the specificities, effector molecules, and physiological roles of these immune cells.

Current projects include

  • Characterization of T cell functional diversity in health and disease
  • Role of IL-10 in maintaining gut homeostasis
  • Role of IL-33 in regulatory T cell function
  • Role of IL-23 in CD4 T cell function 

Techniques

  • Models of inflammatory bowel disease, infectious colitis, and skin inflammation
  • Gene expression profiling, including single-cell RNA sequencing to identify heterogeneity within populations of interest
  • Polychromatic flow cytometry, cell sorting, and ex vivo analysis
  • In vitro primary T cell differentiation and characterization
  • TCR sequencing to determine possible clonality of reactive T cells
  • Intravital microscopy to determine cellular localizations and interaction partners
  • Phospho-proteomic profiling to characterize cytokine induced signaling cascades
  • FISH-flow
  • Luminex assay 

Selected publication

The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature. 2014 Sep 25;513(7519):564-8. doi: 10.1038/nature13577. Epub 2014 Jul 16. 

Myeloid cells

Myeloid Cell Biology

Myeloid cells bridge the innate and adaptive immune response and act as critical sensors within the tissue. Recent work has focused on the critical roles that eosinophils, macrophages, and monocytes play in driving colitis.

Projects

  • Effects of bacterial products on macrophage differentiation and cytokine production
  • Role of IRF-5 in colitis -Role of eosinophils in IBD pathogenesis 
  • Development of induced pluripotent stem (iPS) cell lines

Techniques

  • Gene expression profiling, including single-cell RNA sequencing to identify heterogeneity within populations of interest 
  • In vitro myeloid cell differentiation and characterization 
  • Bacterial phagocytosis and killing assays 
  • Polychromatic flow cytometry, cell sorting, and ex vivo analysis 
  • Models of inflammatory bowel disease and infectious colitis 
  • Luminex assay 

Selected publications

CD11c+ monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23. Mucosal Immunol. 2015 Aug 5. doi: 10.1038/mi.2015.65.

Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis. Immunity. 2015 Jul 21;43(1):187-99. doi: 10.1016/j.immuni.2015.07.008.

Innate lymphoid cells

ILC Biology

Innate lymphoid cells play important roles in innate sensing and cytokine production. They can contribute to protection from infection or pathogenic inflammation.

Projects

  • Role of ILCs in innate colitis
  • ILC orchestration of inflammation 

Techniques

  • Intravital microscopy to determine locations and interaction partners 
  • Immunohistochemistry and immunofluorescence 
  • Flow cytometry/Sorting 
  • Models of inflammatory bowel disease and infectious colitis 
  • Luminex assay 

Selected publication

Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med. 2013 May 6;210(5):917-31. 

Stromal cells

Stromal Cell Biology

Recent data suggests that tissue stromal cells can play an active immunological role in health and disease. We are interested in how stromal cells are modified during inflammation and how they interact with cells of the hematopoietic system.

Projects

  • Identification and characterization of stromal cell subsets in human and murine intestine
  • Identification of altered stromal cell behaviour during chronic intestinal inflammation
  • Identification of mechanisms underpinning perturbed stromal cell biology in inflammatory disease

Techniques

  • Primary culture of human and mouse stromal populations
  • 3D organotypic culture system -Immunohistochemistry and immunofluorescence 
  • Flow cytometry/Sorting 
  • Gene expression profiling 
  • Extracellular matrix deposition and remodeling assays 
  • Luminex assay

Selected publication

CD90(+) Stromal Cells are Non-Professional Innate Immune Effectors of the Human Colonic Mucosa. Front Immunol. 2013 Sep 30;4:307. doi: 10.3389/fimmu.2013.00307.