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Treg cells suppress through a variety of mechanisms. Altman and colleagues show that CTLA-4-PKC-η interaction at the Treg cell immunological synapse is required for contact-dependent suppression by Treg cells (p 465; and News and Views by Wülfing, Tunbridge & Wraith, p 408). The original image shows GFP-tagged PKC-η (green) accumulated at the interface between a Treg cell (red) and an antigenpresenting B cell. Cyan indicates the nuclei. Original image by Tadashi Yokosuka and Takashi Saito. Artwork by Lewis Long.
Live whole-organism vaccines against Plasmodium falciparum malaria and cutaneous leishmaniasis remain the most uniformly effective vaccines against human parasitic diseases. These vaccines are discussed in terms of the requirement for persisting antigen to generate and maintain a protective response.
CTLA-4 is a potent inhibitor of T cell population expansion. The PIX-GIT2-PAK2 complex is recruited to the cytoplasmic domain of CTLA-4 via the kinase PKC-η, which suggests a previously unrecognized aspect of signal transduction via CTLA-4 in immunoregulation.
Although it is generally considered a proinflammatory cytokine, interleukin 6 (IL-6) has anti-inflammatory effects in macrophages by sensitizing them to IL-4 through upregulation of the IL-4 receptor.
Cytokines and other environmental cues influence polarization of CD4+ helper T cells, but the signaling pathways that are involved are less clear. Recent findings show that signaling via an mTORC2-SGK1 kinase axis regulates TH1–TH2 cell-fate polarization.
The role of IL-6 in obesity-associated inflammation remains controversial. Bruening and colleagues identify signaling by IL-6 as an important determinant for the alternative activation of macrophages during inflammation.
The function of the lymphocyte-expressed receptor CD96 is almost entirely unknown. Smyth and colleagues demonstrate that it serves a key role in restraining activation of NK cells in part by competing with the activating receptor CD226 (DNAM-1).
Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4+ T cell lineage integrity by repressing Runx-CBFβ complexes in TH1 cells but not in TH2 cells.
Adaptors of the TRAF family are tumor-necrosis factor receptor–associated factors. So and colleagues show that TRAF5 negative regulates the IL-6 receptor signaling pathway, which limits the induction of proinflammatory CD4+ T cells.
The kinase SGK1 is a downstream target of mTORC2 signaling. Powell and colleagues show that SGK1 regulates TH2 polarization by increasing the stability of the transcription factor JunB and antagonizing IFN-γ expression.
Signaling events at the Treg cell immune synapse remain unknown. Altman and colleagues show that a CTLA-4–PKC-η signaling axis is required for contact-dependent suppression by Treg cells.
The precise mechanisms of the thymic development Treg cells are still being determined. Farrar and colleagues demonstrate that signals from a triumvirate of members of the tumor-necrosis factor receptor superfamily are critical for Treg cell development in the thymus.