title: Molecular control of Tfh-cell differentiation by Roquin family proteins.
abstract: Post-transcriptional gene regulation by RNA-binding proteins is a fast and effective way to adapt gene expression and change cellular responses. These trans-acting factors have been involved in a number of cell fate decisions, and their mutation is often associated with the development of disease. The RNA-binding protein Roquin-1 has been found to be crucial in the maintenance of peripheral tolerance and the prevention of autoimmune disease. This review describes the molecular role of Roquin family proteins in the control of follicular T-helper cell differentiation. Here, we discuss the redundant regulation of Icos and Ox40 costimulatory receptor mRNAs by Roquin-1 and Roquin-2 proteins. A major focus is placed on the distinct activity of Roquin-1 or Roquin-2 proteins in the mouse models of conditional gene targeting. These recent data are then integrated into an interpretation of altered Roquin protein function in the sanroque mouse that expresses the Roquin-1 protein with just one amino acid substitution and, different from the Roquin-1-deficient mouse, develops lupus-like autoimmune disease.
authors.affiliation: Helmholtz Zentrum München, Institute of Molecular Immunology, Munich, Germany. vigo.heissmeyer@helmholtz-muenchen.de
authors.forename: Vigo
authors.initials: V
authors.lastname: Heissmeyer
authors.forename: Katharina U
authors.initials: KU
authors.lastname: Vogel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D053278:OX40 Ligand / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D060889:Inducible T-Cell Co-Stimulator Protein; D053278:OX40 Ligand; D012097:Repressor Proteins; D015534:Trans-Activators; C582114:roquin-2 protein, mouse; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases