The function of NF-κB family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the IκB family. By using a murine model of conditional Bcl-3 overexpression specifically in T cells, we observed impairment in the development of Th2, Th1, and Th17 cells. High expression of Bcl-3 promoted CD4+ T-cell survival, but at the same time suppressed proliferation in response to TCR stimulation, resulting in reduced CD4+ T-cell expansion. As a consequence, T-cell-specific overexpression of Bcl-3 led to reduced inflammation in the small intestine of mice applied with anti-CD3 in a model of gut inflammation. Moreover, impaired Th17-cell development resulted in the resistance of Bcl-3 overexpressing mice to EAE, a mouse model of multiple sclerosis. Thus, we concluded that fine-tuning expression of Bcl-3 is needed for proper CD4+ T-cell development and is required to sustain Th17-cell mediated pathology.
CITATION STYLE
Mufazalov, I. A., Kuschmann, J., Andruszewski, D., Masri, J., Gabriel, L. A., Adams, P., … Waisman, A. (2017). Balanced Bcl-3 expression in murine CD4+ T cells is required for generation of encephalitogenic Th17 cells. European Journal of Immunology, 47(8), 1335–1341. https://doi.org/10.1002/eji.201746933
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