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- Title
The E3 ubiquitin ligase Itch is required for the differentiation of follicular helper T cells.
- Authors
Xiao, Nengming; Eto, Danelle; Elly, Chris; Peng, Guiying; Crotty, Shane; Liu, Yun-Cai
- Abstract
Follicular helper T cells (TFH cells) are responsible for effective B cell-mediated immunity, and Bcl-6 is a central factor for the differentiation of TFH cells. However, the molecular mechanisms that regulate the induction of TFH cells remain unclear. Here we found that the E3 ubiquitin ligase Itch was essential for the differentiation of TFH cells, germinal center responses and immunoglobulin G (IgG) responses to acute viral infection. Itch acted intrinsically in CD4+ T cells at early stages of TFH cell development. Itch seemed to act upstream of Bcl-6 expression, as Bcl-6 expression was substantially impaired in Itch−/− cells, and the differentiation of Itch−/− T cells into TFH cells was restored by enforced expression of Bcl-6. Itch associated with the transcription factor Foxo1 and promoted its ubiquitination and degradation. The defective TFH differentiation of Itch−/− T cells was rectified by deletion of Foxo1. Thus, our results indicate that Itch acts as an essential positive regulator in the differentiation of TFH cells.
- Subjects
UBIQUITIN ligases; CELL differentiation; T helper cells; B cells; BCL-6 protein; CELLULAR immunity; IMMUNOGLOBULIN G; VIRUS diseases; IMMUNOLOGY
- Publication
Nature Immunology, 2014, Vol 15, Issue 7, p657
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2912