Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages

• Published in: iScience 2022-10, Vol.25 (10), p.105151-105151, Article 105151
• Main Authors: Zeng, Qiuming, Tang, Na, Ma, Yilei, Guo, Hui, Zhao, Yixia, Tang, Rong, Yan, Chengkai, Ouyang, Song, Langdon, Wallace Y., Yang, Huan, O’Brien, Matthew C., Zhang, Jian
• Format: Article
• Language: English
• Subjects: Biological sciences; Immune response; Immunology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105151

E3 ubiquitin ligase Cbl-b is involved in the maintenance of a balance between immunity and tolerance. Mice lacking Cbl-b are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a Th17-mediated autoimmune disease. However, how Cbl-b regulates Th17 cell responses remains unclear. In this study, utilizing adoptive transfer and cell type-specific Cblb knockout strains, we show that Cbl-b expression in macrophages, but not T cells or dendritic cells (DCs), restrains the generation of pathogenic Th17 cells and the development of EAE. Cbl-b inhibits IL-6 production by macrophages that is induced by signaling from CARD9-dependent C-type lectin receptor (CLR) pathways, which directs T cells to generate pathogenic Th17 cells. Therefore, our data unveil a previously unappreciated function for Cbl-b in the regulation of pathogenic Th17 responses. [Display omitted] •E3 ubiquitin ligase Cbl-b inhibits EAE disease progression•Cbl-b dampens pathogenic Th17 response via inhibiting macrophage-derived IL-6•Cbl-b controls macrophage-derived IL-6 via a CARD9-dependent manner Biological sciences; Immunology; Immune response