PuSH - Publication Server of Helmholtz Zentrum München

Bertossi, A.* ; Aichinger, M.* ; Sansonetti, P.* ; Lech, M.* ; Neff, F. ; Pal, M.* ; Wunderlich, F.T.* ; Anders, H.J.* ; Klein, L.* ; Schmidt-Supprian, M.*

Loss of Roquin induces early death and immune deregulation but not autoimmunity.

J. Exp. Med. 208, 1749-1756 (2011)
Publ. Version/Full Text Volltext DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
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-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector-like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Helper t-cells; Costimulator messenger-RNA; CRE-LOXP; Mice; Family
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Journal Journal of Experimental Medicine
Quellenangaben Volume: 208, Issue: 9, Pages: 1749-1756 Article Number: , Supplement: ,
Publisher Rockefeller University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)