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

Qiuming Zeng, Na Tang, Yilei Ma, Hui Guo, Yixia Zhao, Rong Tang, Chengkai Yan, Song Ouyang, Wallace Y. Langdon, Huan Yang, Matthew C. O'Brien, Jian Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number105151
Number of pages20
JournalIscience
Volume25
Issue number10
DOIs
Publication statusPublished - 21 Oct 2022

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