Cytokines/chemokines

Thematic

Expression and Regulation of Amphiregulin in Human Regulatory T Cells

Friday, June 16
1:25 PM - 1:40 PM

Regulatory T cells are essential for maintaining immune homeostasis and self-tolerance. Several lines of evidence suggest that adoptive transfer of Tregs can prevent, and in some cases cure, a variety of pathological conditions, from autoimmunity to transplant rejection. In addition to their effects on immune cells, there is also emerging evidence that Tregs have direct effects on tissue repair. Specifically, Tregs in mice promote tissue repair after infection or injury by producing the EGF family member amphiregulin (AREG) under the control of the alarmins IL-18 and IL-33. We investigated expression and regulation of AREG in human peripheral blood Tregs. TCR stimulation of Tregs (CD4+CD25hiCD127lo) increased AREG mRNA and protein, particularly in the HLA-DR subset, but levels were lower than in their Tconv counterparts. In contrast to reports from murine Tregs, IL-18 and IL-33 did not modulate human Treg production of AREG. Ex vivo Tregs expressed IL-18Rα, but expression of IL-33Rα (ST2) was not detectable. To more accurately measure human ST2 expression, we used phage display to generate a series of anti-ST2 mAbs. Experiments in ST2-transfected HEK-293T and transduced CD4+ T cells revealed several candidate anti-ST2 mAbs that were superior to commercially available mAbs for flow cytometric detection of human ST2. Experiments to better define the localization and biology of human ST2+ Tregs are in progress. Knowledge of whether human Tregs produce AREG is important to understand their potential to mediate tissue repair in addition to immunosuppression when used as a cell-based therapy.

Avery J. Lam

The University of British Columbia

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Sabine M. Ivison

University of British Columbia

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Anne M. Pesenacker

University of British Columbia

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Guy Charron

Université de Montréal

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Haiming Huang

University of Toronto

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iGenoMed Consortium

iGenoMed Consortium

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Sachdev S. Sidhu

University of Toronto

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James G. Pan

University of Toronto

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John D. Rioux

Université de Montréal

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Megan K. Levings

Professor
University of British Columbia
University of British Columbia

Megan K. Levings, PhD
Professor, Dept of Surgery, University of British Columbia
Head, Childhood Diseases Theme, BC Children’s Hospital Research Institute

Dr. Megan Levings has been in the UBC Department of Surgery since 2003 when she was recruited back to Canada as a Canada Research Chair in Transplantation. In 2011 she joined the BC Children’s Hospital Research Institute where she now heads the Childhood Diseases Theme. Dr. Levings’ scientific career started with summer research positions in a fruit fly genetics lab at Simon Fraser University. She then did her graduate training in the genetics program with Dr. John Schrader at UBC. In 1999 she joined Dr. Maria Grazia Roncarolo's lab in Milan, Italy, undertaking postdoctoral training in the emerging area of immune regulation. She was among the first groups to show that a special kind of white blood cell, known as a T regulatory cell, could be used as a therapy to stop harmful immune responses. She continues this line of research at UBC, and is now internationally recognized in the field of human immunology and chairs the Federation of Clinical Immunology Societies Centres of Excellence. She leads a vibrant group of trainees and staff who are researching how to use T regulatory cells to replace conventional immunosuppression in the context of transplantation and autoimmunity.

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Expression and Regulation of Amphiregulin in Human Regulatory T Cells



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