The E3 Ubiquitin Ligase Itch is Required for B-cell Development

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jan 25

PMID 30674954

Citations 9

Authors

Xiaoling Liu

Yu Zhang

Yinxiang Wei

Zhiding Wang

Gaizhi Zhu

Ying Fang

Bing Zhai

Ruonan Xu

Gencheng Han

Guojiang Chen

He Xiao

Chunmei Hou

Beifen Shen

Yan Li

Ning Ma

Renxi Wang

Affiliations

Soon will be listed here.

Abstract

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 IgMIgDB 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.

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