Journal article
The ubiquitin ligase Cul5 regulates CD4+ T cell fate choice and allergic inflammation
NATURE COMMUNICATIONS, v 13(1), 2786
19 May 2022
PMID: 35589717
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cytokine signaling influences the differentiation of CD4(+) T cells into varying functional subsets. Here the authors show that an E3 ubiquitin ligase Cul5 alters T(H)2 and T(H)9 development and absence of Cul5 in T cells results in higher levels of allergy-associated IL-4 and IL-9 secreting T cells. Antigen encounter directs CD4(+) T cells to differentiate into T helper or regulatory cells. This process focuses the immune response on the invading pathogen and limits tissue damage. Mechanisms that govern T helper cell versus T regulatory cell fate remain poorly understood. Here, we show that the E3 ubiquitin ligase Cul5 determines fate selection in CD4(+) T cells by regulating IL-4 receptor signaling. Mice lacking Cul5 in T cells develop Th2 and Th9 inflammation and show pathophysiological features of atopic asthma. Following T cell activation, Cul5 forms a complex with CIS and pJak1. Cul5 deletion reduces ubiquitination and subsequent degradation of pJak1, leading to an increase in pJak1 and pSTAT6 levels and reducing the threshold of IL-4 receptor signaling. As a consequence, Cul5 deficient CD4(+) T cells deviate from Treg to Th9 differentiation in low IL-4 conditions. These data support the notion that Cul5 promotes a tolerogenic T cell fate choice and reduces susceptibility to allergic asthma.
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Details
- Title
- The ubiquitin ligase Cul5 regulates CD4+ T cell fate choice and allergic inflammation
- Publication Details
- NATURE COMMUNICATIONS, v 13(1), 2786
- Publisher
- NATURE PORTFOLIO; BERLIN
- Grant note
- We thank the Proteomics, Flow Cytometry and Pathology Core at Children's Hospital of Philadelphia. This work was supported by the National Institutes of Health Grants (R01AI148240) to P.M.O.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000798347800015
- Scopus ID
- 2-s2.0-85130322033
- Other Identifier
- 991021861284604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology