Oral Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

A Novel Langerin Expressing Type 2-Conventional Dendritic Cell Is Significantly Decreased In Crohn’s Disease (#89)

Chloe M Doyle 1 2 3 4 , Kirstie Bertram 2 3 4 , Jake Rhodes 1 2 4 , Erica Vine 2 3 4 , Heeva Baharlou 2 3 , Martijn Gosselink 1 3 5 , Angelina Di Re 1 3 5 , Geoffrey Collins 1 3 5 , Faizur Reza 1 3 5 , James Toh 1 3 5 , Nimalan Pathma-Nathan 1 3 5 , Golo Ahlenstiel 6 7 8 , Grahame Ctercteko 1 3 5 , Anthony Cunningham 2 3 , Andrew Harman 1 2 4 , Scott Byrne 1 4
  1. Centre for Immunology and Allergy Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
  3. Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
  4. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
  5. Department of Colorectal Surgery, Westmead Hospital, Westmead, NSW, Australia
  6. Storr Liver Centre, The Westmead Institute for Medical Research, Westmead, NSW, Australia
  7. Blacktown Clinical School, Western Sydney University, Blacktown, NSW, Australia
  8. Blacktown Hospital, Western Sydney Local Area Health District (WSLHD), Blacktown, NSW, Australia

Crohn’s disease is an auto-inflammatory condition of the gastrointestinal tract that primarily affects young individuals with an increasing incidence rate. There is no cure for Crohn’s disease and current treatment-options are limited. Targeting the cells and molecules of the immune system represents a promising approach. We have therefore conducted an in-depth study of the immune cells associated with Crohn’s disease.

Our group has privileged access to large human ileum explants as well as lymph nodes isolated from patients undergoing surgery to remove Crohn’s affected tissue. We have designed and optimised enzymatic tissue digestion protocols to isolate these cells in an immature state with minimal receptor cleavage. We have also developed high-parameter flow cytometry panels to comprehensively identify and characterise all known subsets of mononuclear phagocytes (MNP), innate lymphoid cells, mucosal-associated invariant T cells, natural killer cells and T and B lymphocytes.

We have discovered that the newly described Langerin+ type 2-conventional dendritic cell (cDC2) is significantly decreased in Crohn’s affected ileum compared to healthy ileum. Furthermore, we have shown this decrease corresponds with lower TGF-b levels, a known driver of Langerin expression. After 7 days of co-culture, sorted Langerin+ cDC2 induced significantly higher levels of IL-17 and IL-22 in allogenic naïve CD4+ T cells compared to other MNP subsets, including cDC2 which did not express Langerin. These differentiated T cells expressed high levels of RORt and aryl hydrocarbon receptor (AHR) – transcription factors that are associated with CD4+ T helper 17 cells, implying that they may play a crucial role in intestinal barrier repair and regeneration that is absent in Crohn’s disease. Together these results suggest that Langerin+ cDC2 may have an anti-inflammatory role in human tissue and their reduction in Crohn’s disease may contribute to the pathogenesis of this disease, highlighting a potential therapeutic target for Crohn’s disease.