Balanced Bcl-3 expression in murine CD4(+) Tcells is required for generation of encephalitogenic Th17 cells

作者：Mufazalov Ilgiz A; Kuschmann Janina; Andruszewski David; Masri Joumana; Gabriel Laureen A; Adams Petra; Reissig Sonja; Hoevelmeyer Nadine; Waisman Ari

来源：European Journal of Immunology, 2017, 47(8): 1335-1341.

DOI：10.1002/eji.201746933

• Bcl-3
• Tcells
• Th17 cells
• EAE
• anti-CD3 treatment
• NF-B
• MOG

The function of NF-kappa B family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the I kappa B 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.

• 出版日期2017-8