ICOS is an inducible T-cell co-stimulator with homology to CD28 []. CD28 and ICOS function similarly during expansion, survival and differentiation of T cells. They are necessary for proper IgG responses. However, CD28 induces IL-2 production, while ICOS is more potent in the induction of IL-10 production [].
Roquin-1 (RC3H1) is a post-transcriptional repressor required to repress follicular helper T cells (Tfh) and autoimmunity []. It binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. For instance, it controls ICOS (inducible costimulator) expression through binding to the 3' UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression []. Besides ICOS, it also represses Ox40 and interferon-gamma in T cells, and this helps to prevent inappropriate T cell activation and Tfh cell differentiation [, ].Roquin-1 and its paralogue, Roquin-2 (Rc3h2), have been found to redundantly repress the mRNAs controlling T follicular helper cells and systemic inflammation [, ]. Tfhs are helper T-cells specialised in facilitating B-cell responses [].
