The zinc finger protein 36-like 2, ZFP36L2, is a member of a small family of 
RNA-binding proteins composed by ZFP36 (also known as tristetraprolin, TTP), 
ZFP36L1 and ZFP36L2 in humans, with corresponding murine orthologs. These 
proteins bind to adenine uridine-rich element (ARE) in the 3'untranslated region 
of target messenger RNA and stimulate target degradation. ZFP36 functions as an 
anti-inflammatory modulator in murine models of inflammatory diseases by 
down-regulating the production of inflammatory cytokines such as tumor necrosis 
factor-α. However, how ZFP36L1 and ZFP36L2 alter the function of CD4+ T cells is 
not completely understood. We addressed this issue by searching for the target 
genes of ZFP36L2 by comprehensive transcriptome analysis. We observed that 
ZFP36L2 is highly expressed in naïve CD4+ T cells; however, when CD4+ T cells 
are stimulated through their T cell receptors, ZFP36L2 expression is rapidly 
reduced in both humans and mice. Among CD4+ T cell populations, the expression 
levels of ZFP36L2 in regulatory T cells (Tregs) were significantly lower than 
those in naïve or effector CD4+ T cells. RNA-sequence analysis revealed that the 
forced expression of ZFP36L2 decreased Ikzf2 (encoding Helios) expression in 
Foxp3+ Tregs and inhibited the ability of induced Tregs (iTregs). ZFP36L2 
directly bound to and destabilized the 3'untranslated region of Ikzf2 mRNA, 
which contains AU-rich elements. These results indicate that ZFP36L2 reduces the 
expression of Ikzf2 and suppresses iTreg function, raising the interesting 
possibility that the inhibition of ZFP36L2 in iTregs could be a therapeutic 
strategy for autoimmune diseases.