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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...

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Autores principales: Mahfooz, Najmus S., Merling, Marlena R., Claeys, Tiffany A., Dowling, Jack W., Forero, Adriana, Robinson, Richard T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAI 2023
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
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author Mahfooz, Najmus S.
Merling, Marlena R.
Claeys, Tiffany A.
Dowling, Jack W.
Forero, Adriana
Robinson, Richard T.
author_facet Mahfooz, Najmus S.
Merling, Marlena R.
Claeys, Tiffany A.
Dowling, Jack W.
Forero, Adriana
Robinson, Richard T.
author_sort Mahfooz, Najmus S.
collection PubMed
description 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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spelling pubmed-105801222023-10-23 Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2 Mahfooz, Najmus S. Merling, Marlena R. Claeys, Tiffany A. Dowling, Jack W. Forero, Adriana Robinson, Richard T. Immunohorizons Adaptive Immunity 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. AAI 2023-06-08 /pmc/articles/PMC10580122/ /pubmed/37289499 http://dx.doi.org/10.4049/immunohorizons.2300039 Text en Copyright © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the CC BY 4.0 Unported license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Adaptive Immunity
Mahfooz, Najmus S.
Merling, Marlena R.
Claeys, Tiffany A.
Dowling, Jack W.
Forero, Adriana
Robinson, Richard T.
Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title_full Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title_fullStr Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title_full_unstemmed Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title_short Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
title_sort human il-35 inhibits the bioactivity of il-12 and its interaction with il-12rβ2
topic Adaptive Immunity
url 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
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