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Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
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, trigger...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580122/ https://www.ncbi.nlm.nih.gov/pubmed/37289499 http://dx.doi.org/10.4049/immunohorizons.2300039 |
Sumario: | 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. |
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