Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 18, Issue 7, Pages 1729-1738Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-0384-0
Keywords
Sox12; Asthma; GATA3; Th2; ubiquitination
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology
- Japanese Government
- LGS (Leading Graduate School at Chiba University) Program, MEXT
- Institute for Global Prominent Research, Chiba University, Japan
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Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation and attenuates HDM-induced allergic inflammation.
Allergic asthma that is caused by inhalation of house dust mites (HDMs) is mainly mediated by Th2 cells. Recently, the roles of Sox (SRY-related high-mobility-group (HMG)-box) family members in various immune responses have been investigated. However, the roles of Sox12, a member of the SoxC group, in Th2 cell differentiation and allergic airway inflammation, remain unknown. We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation. In vivo, HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12(-/-) mice compared with those in control Sox12(+/-) mice. In vitro, Sox12(-/-) CD4(+) T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12(+/-) CD4(+) T cells. Importantly, forced expression of Sox12 decreased the protein levels of GATA3 in CD4(+) T cells under Th2 conditions without affecting mRNA expression. Furthermore, Sox12 induced degradation of GATA3 through the proteasome pathway in CD4(+) T cells. Consistently, Sox12 enhanced ubiquitination of GATA3, which was mediated by the E3 ligase Fbw7. Finally, we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4(+) T cells. Taken together, these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation, and attenuates HDM-induced allergic inflammation.
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