Author: Renauld, Jean-Christophe ; Bianchi, Roberta ; Belladonna, Maria Laura ; Puccetti, Paolo ; Fioretti, Maria Cristina ; Grohmann, Ursula ; Vacca, Carmine ; Orabona, Ciriana ; Fallarino, Francesca

AbstractIL-23 is a recently discovered heterodimeric cytokine that shares biological properties with proinflammatory cytokines. The biologically active heterodimer consists of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess biological activities on T cells that are similar as well distinct from those of IL-12. We have constructed single-chain IL-23 and IL-12 fusion proteins (IL-23-Ig and IL-12-Ig) and have compared the two recombinant proteins for effects on murine dendritic cells (DC). Here we show that the IL-23-Ig can bind a significant proportion of splenic DC of both the CD8α− and CD8α+ subtypes. Furthermore, IL-23and IL-12-Ig exert biological activities on DC that are only in part overlapping. While both proteins induce IL-12 production from DC, only IL-23-Ig can act directly on CD8α+ DC to promote immunogenic presentation of an otherwise tolerogenic tumor peptide. In addition, the in vitro effects of IL-23-Ig did not appear to require IL-12Rβ2 or to be mediated by the production of IL-12. These data may establish IL-23 as a novel cytokine with major effects on APC.

15 Aug 2000·The Journal of ImmunologyQ2 · MEDICINE

IL-4 Is a Mediator of IL-12p70 Induction by Human Th2 Cells: Reversal of Polarized Th2 Phenotype by Dendritic Cells

Q2 · MEDICINE

Article

Author: de Jong, Esther C. ; van Eijk, Marco ; Kapsenberg, Martien L. ; Schuitemaker, Joost H. N. ; Vieira, Pedro L. ; Smits, Hermelijn H. ; Kaliński, Paweł ; Wierenga, Eddy A.

AbstractIL-12 is a key inducer of Th1-associated inflammatory responses, protective against intracellular infections and cancer, but also involved in autoimmune tissue destruction. We report that human Th2 cells interacting with monocyte-derived dendritic cells (DC) effectively induce bioactive IL-12p70 and revert to Th0/Th1 phenotype. In contrast, the interaction with B cells preserves polarized Th2 phenotype. The induction of IL-12p70 in Th2 cell-DC cocultures is prevented by IL-4-neutralizing mAb, indicating that IL-4 acts as a Th2 cell-specific cofactor of IL-12p70 induction. Like IFN-γ, IL-4 strongly enhances the production of bioactive IL-12p70 heterodimer in CD40 ligand-stimulated DC and macrophages and synergizes with IFN-γ at low concentrations of both cytokines. However, in contrast to IFN-γ, IL-4 inhibits the CD40 ligand-induced production of inactive IL-12p40 and the production of either form of IL-12 induced by LPS, which may explain the view of IL-4 as an IL-12 inhibitor. The presently described ability of IL-4 to act as a cofactor of Th cell-mediated IL-12p70 induction may allow Th2 cells to support cell-mediated immunity in chronic inflammatory states, including cancer, autoimmunity, and atopic dermatitis.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced breast cancer	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023
Advanced gastric carcinoma	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023
Advanced Head and Neck Carcinoma	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023
Advanced Lung Non-Small Cell Carcinoma	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023
Colorectal Cancer	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023
Melanoma	IND Approval	CN	Stemirna Therapeutics Co., Ltd.Startup	07 Jun 2023

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