Cytokines/chemokines

Oral

Expression and Regulation of Amphiregulin in Human Regulatory T Cells

Friday, June 16
6:15 PM - 7:30 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

                    University of British Columbia

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                      Expression and Regulation of Amphiregulin in Human Regulatory T Cells



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