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

doi:10.1016/j.isci.2022.105151

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

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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, …

iScience, Vol.25(10), 105151

10/01/2022

DOI: 10.1016/j.isci.2022.105151

PMCID: PMC9523381

PMID: 36185364

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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.

Biological Sciences

Immunology

Immune response

Details

Title: Subtitle: Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages
Creators: Qiuming Zeng
Na Tang
Yilei Ma - University of Iowa
Hui Guo
Yixia Zhao
Rong Tang
Chengkai Yan - University of Iowa
Song Ouyang
Wallace Y. Langdon - The University of Western Australia
Huan Yang - Xiangya Hospital Central South University
Matthew C. O’Brien - Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
Jian Zhang
Resource Type: Journal article
Publication Details: iScience, Vol.25(10), 105151
DOI: 10.1016/j.isci.2022.105151
PMID: 36185364
PMCID: PMC9523381
NLM abbreviation: iScience
ISSN: 2589-0042
eISSN: 2589-0042
Publisher: Elsevier
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AI090901, R01 AI121196, R01 AI123253; DOI: 10.13039/501100004543, name: China Scholarship Council
Language: English
Date published: 10/01/2022
Academic Unit: Pathology
Record Identifier: 9984303288002771

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