Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.

Autor:	Mahfooz NS; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Merling MR; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Claeys TA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Dowling JW; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Forero A; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Robinson RT; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2023 Jun 01; Vol. 7 (6), pp. 431-441.
DOI:	10.4049/immunohorizons.2300039
Abstrakt:	IL-35 is an immunosuppressive cytokine with roles in cancer, autoimmunity, and infectious disease. In the conventional model of IL-35 biology, the p35 and Ebi3 domains of this cytokine interact with IL-12Rβ2 and gp130, respectively, on the cell surface of regulatory T and regulatory B cells, triggering their suppression of Th cell activity. Here we use a human IL-12 bioactivity reporter cell line, protein binding assays, and primary human Th cells to demonstrate an additional mechanism by which IL-35 suppresses Th cell activity, wherein IL-35 directly inhibits the association of IL-12 with its surface receptor IL-12Rβ2 and downstream IL-12-dependent activities. IL-12 binding to the surface receptor IL-12Rβ1 was unaffected by IL-35. These data demonstrate that in addition to acting via regulatory T and regulatory B cells, human IL-35 can also directly suppress IL-12 bioactivity and its interaction with IL-12Rβ2. (Copyright © 2023 The Authors.)
Databáze:	MEDLINE
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