First hypotheses regarding the role of TFH cells in SLE development are based on studies using mice deficient for Roquin1 (a negative regulator of ICOS mRNA stability) in which an excessive number of TFH cells and GC reactions and high levels of IL-21 are associated with a lupus-like phenotype [50, 51]. Here, ICOS is linked to systemic lupus erythematosus.