Loss of Roquin induces early death and immune deregulation but not autoimmunity
Arianna Bertossi, Martin Aichinger, Paola Sansonetti, Maciej Lech, Frauke Neff, Martin Pal, F Thomas Wunderlich, Hans-Joachim Anders, Ludger Klein, Marc Schmidt-Supprian
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2011
The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell-intrinsic and -extrinsic mechanisms, which itself was not sufficient to break self..View full abstract
Awarded by Deutsche Forschungsgemeinschaft (DFG)
This study was supported by Emmy Noether grant SCHM2440 from the Deutsche Forschungsgemeinschaft (DFG) and a grant from the Thyssen Foundation to M. Schmidt-Supprian. H.-J. Anders was supported by DFG grant AN372/10-1, and M. Aichinger and L. Klein were supported by DFG grant KL1228/2-1.