TRIM38 Inhibits TNFα- and IL-1β-Triggered NF-κB Activation by Mediating Lysosome-Dependent Degradation of TAB2/3 Investigators identified tripartite-motif protein 38 (TRIM38) as a critical negative regulator of TNFα- and IL-1β-triggered signaling. Overexpression of TRIM38 inhibited activation of NF-κB and induction of downstream cytokines following TNFα and IL-1β stimulation, whereas knockdown or knockout of TRIM38 had the opposite effects. [Proc Natl Acad Sci USA] Abstract Alarmin IL-33 Acts as an Immunoadjuvant to Enhance Antigen-Specific Tumor Immunity Two biologically active isoforms of IL-33 exist that are full-length or mature, but the ability of either isoform to function as a vaccine adjuvant that influences CD4 Th1 or CD8 T cell immune responses is not defined. Researchers showed that both IL-33 isoforms are capable of enhancing potent antigen-specific effector and memory T cell immunity in vivo in a DNA vaccine setting. [Cancer Res] Abstract | Press Release IL-17-Producing NKT Cells Depend Exclusively on IL-7 for Homeostasis and Survival Scientists showed that natural killer T (NKT)17 cells deviate from other NKT cells in their survival requirements. In contrast to conventional NKT cells that are maintained by IL-15, RORγt+ NKT cells are IL-15 independent and instead rely completely on IL-7. [Mucosal Immunol] Abstract Conventional CD4+ T Cells Regulate IL-22-Producing Intestinal Innate Lymphoid Cells The authors found that CD4+ T cells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3γ and Reg3β. RAG1−/− mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4+ T cells. [Mucosal Immunol] Abstract Excess IL-1 Signaling Enhances the Development of Th17 Cells by Downregulating TGF-β-Induced Foxp3 Expression The authors found that IL-21 production was increased in the lymph nodes of IL-1R antagonist-deficient (Il1rn−/−) mice, naive Il6−/− CD4+ T cells differentiated into Th17 cells when cultured with TGF-β and IL-21, and the differentiation was greatly enhanced when IL-1 was added to the culture. [J Immunol] Abstract IL-21 Contributes to Fatal Inflammatory Disease in the Absence of Foxp3+ T Regulatory Cells To distinguish the effect of IL-21 on the immune system from that of its effect on T regulatory cells (Tregs), investigators analyzed the role of IL-21/IL-21R signaling in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2-dependent Foxp3 Tregs and suffer from a fatal multiorgan inflammatory disease. [J Immunol] Abstract A Requirement of Dendritic Cell-Derived Interleukin-27 for the Tumor Infiltration of Regulatory T Cells Scientists demonstrated that in the absence of dendritic cell-derived interkeukin (IL)-27, regulatory T cells (Foxp3+CD4+) were decreased significantly in transplanted B16 melanoma, transplanted EL-4 lymphoma, and MCA-induced fibrosarcoma by using IL-27p28 conditional KO mice. [J Leukoc Biol] Abstract |