Lam, AJ; MacDonald, KN; Pesenacker, AM; Juvet, SC; Morishita, KA; Bressler, B; iGenoMed Consortium, .; ... Levings, MK; + view all Lam, AJ; MacDonald, KN; Pesenacker, AM; Juvet, SC; Morishita, KA; Bressler, B; iGenoMed Consortium, .; Pan, JG; Sidhu, SS; Rioux, JD; Levings, MK; - view fewer (2019) Innate Control of Tissue-Reparative Human Regulatory T Cells. The Journal of Immunology , 202 (8) pp. 2195-2209. 10.4049/jimmunol.1801330.

Text Pesenacker_Innate Control of Tissue-Reparative Human Regulatory T Cells_AAM.pdf - Accepted Version Access restricted to UCL open access staff Download (12MB)

Abstract

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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