| Autor: |
Kumar, Binod, Field, Natania S., Kim, Dale D., Dar, Asif A., Chen, Yanqun, Suresh, Aishwarya, Pastore, Christopher F., Hung, Li-Yin, Porter, Nadia, Sawada, Keisuke, Shah, Palak, Elbulok, Omar, Moser, Emily K., Herbert, De'Broski R., Oliver, Paula M. |
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| Zdroj: |
Nature Communications; 5/19/2022, Vol. 13 Issue 1, p1-14, 14p |
| Abstrakt: |
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. Cytokine signaling influences the differentiation of CD4+ T cells into varying functional subsets. Here the authors show that an E3 ubiquitin ligase Cul5 alters TH2 and TH9 development and absence of Cul5 in T cells results in higher levels of allergy-associated IL-4 and IL-9 secreting T cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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