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The E3 ubiquitin ligase Itch is required for B-cell development

The E3 ubiquitin ligase Itch interacts with Foxo1 and targets it for ubiquitination and degradation during follicular helper T-cell differentiation, whereas the transcription factor Foxo1 plays a critical role in B-cell development. Thus, we proposed that Itch mediates B-cell differentiation. Unexpe...

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Detalles Bibliográficos
Autores principales: Liu, Xiaoling, Zhang, Yu, Wei, Yinxiang, Wang, Zhiding, Zhu, Gaizhi, Fang, Ying, Zhai, Bing, Xu, Ruonan, Han, Gencheng, Chen, Guojiang, Xiao, He, Hou, Chunmei, Shen, Beifen, Li, Yan, Ma, Ning, Wang, Renxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344599/
https://www.ncbi.nlm.nih.gov/pubmed/30674954
http://dx.doi.org/10.1038/s41598-018-36844-9
Descripción
Sumario:The E3 ubiquitin ligase Itch interacts with Foxo1 and targets it for ubiquitination and degradation during follicular helper T-cell differentiation, whereas the transcription factor Foxo1 plays a critical role in B-cell development. Thus, we proposed that Itch mediates B-cell differentiation. Unexpectedly, we found that Itch deficiency downregulated Foxo1 expression in B cells. Itch cKO (conditional knock out in B cells) mice had fewer pro-B cells in the bone marrow, more small resting IgM(−)IgD(−)B cells in the periphery, and lower B-cell numbers in the lymph nodes through decreased Foxo1-mediated IL-7Rα, RAG, and CD62L expression, respectively. Importantly, Itch deficiency reduced Foxo1 mRNA expression by up-regulating JunB-mediated miR-182. Finally, Foxo1 negatively regulated JunB expression by up-regulating Itch. Thus, we have identified a novel regulatory axis between Itch and Foxo1 in B cells, suggesting that Itch is essential for B-cell development.