TY - JOUR
T1 - Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2
AU - Mahfooz, Najmus S.
AU - Merling, Marlena R.
AU - Claeys, Tiffany A.
AU - Dowling, Jack W.
AU - Forero, Adriana
AU - Robinson, Richard T.
N1 - Publisher Copyright:
Copyright © 2023 The Authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85162784114&partnerID=8YFLogxK
U2 - 10.4049/immunohorizons.2300039
DO - 10.4049/immunohorizons.2300039
M3 - Article
C2 - 37289499
AN - SCOPUS:85162784114
SN - 2573-7732
VL - 7
SP - 431
EP - 441
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 6
ER -