Journal
JOURNAL OF IMMUNOLOGY
Volume 202, Issue 8, Pages 2195-2209Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1801330
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Funding
- Canadian Institutes of Health Research [FDN-154304]
- iGenoMed Consortium from Genome Quebec
- Genome Canada
- Government of Canada
- Ministere de l'Enseignement Superieur, de la Recherche, de la Science et de la Technologie du Quebec
- Canadian Institutes of Health Research (Institute of Infection and Immunity)
- Canadian Institutes of Health Research (Institute of Genetics)
- Canadian Institutes of Health Research (Institute of Nutrition, Metabolism and Diabetes)
- Genome British Columbia
- Crohn's Colitis Canada
- Agilent Technologies
- BC Children's Hospital Research Institute graduate award
- Juvenile Diabetes Research Foundation postdoctoral fellowship
- Arthritis Research UK career development fellowship
- BC Children's Hospital Research Institute
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Regulatory T cell (Treg) therapy is a potential curative approach for a variety of immune-mediated conditions, including autoimmunity and transplantation, in which there is pathological tissue damage. In mice, IL-33R (ST2)-expressing Tregs mediate tissue repair by producing the growth factor amphiregulin, but whether similar tissue-reparative Tregs exist in humans remains unclear. We show that human Tregs in blood and multiple tissue types produced amphiregulin, but this was neither a unique feature of Tregs nor selectively upregulated in tissues. Human Tregs in blood, tonsil, synovial fluid, colon, and lung tissues did not express ST2, so ST2(+) Tregs were engineered via lentiviral-mediated overexpression, and their therapeutic potential for cell therapy was examined. Engineered ST2(+) Tregs exhibited TCR-independent, IL-33-stimulated amphiregulin expression and a heightened ability to induce M2-like macrophages. The finding that amphiregulin-producing Tregs have a noneffector phenotype and are progressively lost upon TCR-induced proliferation and differentiation suggests that the tissue repair capacity of human Tregs may be an innate function that operates independently from their classical suppressive function.
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