We also found enhanced production of IFN-γ and IL-17 in Egr-2 CKO mice after IL-27 stimulation. Egr-2 CKO mice develop autoimmune disease characterized by the accumulation of IFN-γ and IL-17-producing CD4+ T cells, and massive infiltration of T cells into multiple organs. The expressions of T-bet, a Th1 transcription factor, IL-6, IL-21, and IL-23,

which can induce Th17 differentiation in CD4+ T cells, were not altered in aged Egr-2 CKO mice [30]. Blimp-1 CKO mice develop severe colitis with age and Blimp-1-deficient CD4+ T cells have been shown to produce more IFN-γ than WT after stimulation with PMA plus ionomycin or with TCR plus IL-2 [18]. Recently, Lin et al. [43] reported that NOD-background Blimp-1-deficient selleckchem CD4+ T cells exhibit significantly enhanced IL-17 production selleck products in a steady-state as well as in a Th17-polarizing condition. These observations indicate that increased IFN-γ and IL-17 production in IL-27-stimulated Egr-2-deficient CD4+ T cells may be a direct consequence of reduced Egr-2-Blimp-1 signaling. Although Egr-2 CKO mice did not exhibit colitis, a single-nucleotide polymorphism in a locus at chromosome 10q21, which was identified by genome-wide analysis to have a strong relationship with Crohn’s disease susceptibility, exists in a

strong linkage disequilibrium region of Egr-2 [44, 45]. In summary, we have shown that Egr-2 mediates IL-27-induced IL-10 production through Blimp-1 transcription in CD4+ T cells. Additionally, IFN-γ and IL-17

production by IL-27 was reciprocally regulated by Egr-2. Egr-2 may play a crucial role in maintaining the balance between regulatory and inflammatory cytokines. Our observation could contribute to the elucidation of the molecular regulation of IL-10 production in CD4+ T cells. C57BL/6 mice and Prdm1-floxed mice were purchased from Japan SLC and The Jackson Laboratory, respectively. Blimp-1 CKO mice were generated by crossing Prdm1-floxed mice with CD4-Cre transgenic mice in which Cre-induced recombination was detected 4-Aminobutyrate aminotransferase only in CD4+ T cells. Egr-2 CKO mice were generated by crossing Egr-2-floxed mice [46] with CD4-Cre transgenic mice. TEα TCR transgenic mice were purchased from The Jackson Laboratory. WSX-1 deficient (WSX-1 KO) mice were prepared as described previously [47]. STAT1 KO mice were purchased from Taconic. STAT3 CKO mice (STAT3fl/fl-CD4-Cre+) were generated by crossing STAT3-floxed mice with CD4-Cre transgenic mice. CD4-Cre transgenic mice (line 4196), originally generated by Wilson and colleagues [48], were purchased from Taconic. All mice were used at 7–10 weeks of age. All animal experiments were conducted in accordance with Institutional and National Guidelines. The following reagents were purchased from BD Pharmingen: purified mAbs for CD3ε (145–2C11) and CD28 (37.