The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and pathogenicity of auto-immune T cells

• Published in: Immunity (Cambridge, Mass.) Vol. 41; no. 4; pp. 555 - 566
• Main Authors: Tang, Wanhu, Wang, Hongshan, Claudio, Estefania, Tassi, Ilaria, Ha, Hye-lin, Saret, Sun, Siebenlist, Ulrich
• Format: Journal Article
• Language: English
• Published: 16-10-2014
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2014.09.017

Bcl-3 is an atypical member of the IκB family that modulates transcription in the nucleus via association with p50 (NF-κB1) or p52 (NF-κB2) homodimers. Despite evidence attesting to the overall physiologic importance of Bcl-3, little is known about its cell-specific functions or mechanisms. Here we demonstrate a T cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed to induce disease in T cell transfer-induced colitis and experimental autoimmune encephalomyelitis. The protection against disease correlated with a decrease in Th1 cells that produced the cytokines IFNγ- and GM-CSF, and an increase in Th17 cells. Although differentiation into Th1 cells was not impaired in the absence of Bcl-3, differentiated Th1 cells converted to less pathogenic Th17-like cells, in part via mechanisms involving expression of the RORγt transcription factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by blocking conversion to Th17-like cells, revealing a unique type of regulation that shapes adaptive immunity.