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

Expression of CD49f defines subsets of human regulatory T cells with divergent transcriptional landscape and function that correlate with ulcerative colitis disease activity (#214)

Harshi Weerakoon 1 , Jasmin Straube 1 , Katie Lineburg 1 , Leanne Cooper 1 , Steven Lane 1 , Corey Smith 1 , Saleh Alabbas 2 , Jakob Begun 2 , John Miles 3 , Michelle Hill 1 , Ailin Lepletier 4
  1. The Council of the Queensland Institute of Medical, Herston, Queensland, Australia
  2. Mater Research Institute, University of Queensland, Brisbane, QLD, Australia
  3. Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Cairns, QLD, Australia
  4. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia

Background: Immune suppression through regulatory T cells (Treg) is pivotal for maintaining body homeostasis, controlling exaggerated immune responses against pathogens, and the prevention of immune cells attacking healthy tissue in the cases of autoimmunity, allograft reaction and foetal rejection during pregnancy1. In this regard, adoptive Treg therapy is being trialled for treatment of different autoimmune disorders, including inflammatory bowel diseases (IBD)2. While the overall Treg cell population is defined as CD4+ T cells bearing a CD25highFoxP3highCD127- phenotype, Treg found in peripheral circulation are highly heterogenic and have diverse function3,4. In-depth understanding of the biological variability of Treg in the human blood may be required to improve IBD immune monitoring and treatment strategies.

Methods: Through a combination of quantitative proteomic, multiparametric flow cytometry, RNA-sequencing data analysis and functional assays on Treg enriched from the blood of ulcerative colitis (UC) patients and healthy controls, we investigated the association between CD49f expression, Treg phenotype and function, and UC disease activity.

Results: High-dimensional analysis and filtering defined two distinct subsets of human Treg based on the presence or absence of CD49f with divergent transcriptional landscape and functional activities. CD49f negative (CD49f-) Treg are enriched for functional Treg markers and present significantly increased suppressive capacity.  In contrast, CD49fhigh Treg display a pro-inflammatory Th17-like phenotype and accumulate in the blood of patients with UC. Dysregulation on CD49f Treg subsets in patients with UC correlate with disease activity.

Conclusion: Overall our findings uncover the importance of CD49f expression on Treg in physiological immunity and in pathological autoimmunity.

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