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Natural killer (NK) cells can acquire ‘memory’ signatures. Sun and colleagues examine the dynamic ATAC-seq and functional RNA-seq changes observed upon generation of NK cell memory and show distinct roles for transcription factors STAT1 and STAT4.
Signaling via the cytokine IL-9 receptor regulates humoral recall responses. Kitamura and colleagues report that IL-9 triggers memory B cells to proliferate and terminally differentiate into antibody-secreting cells rather than re-entering germinal centers.
Evidence of protective and homeostatic roles for IgE is relatively limited. Strid and colleagues demonstrate that γδ T cells induce switching to IgE that provides protection against experimentally induced epithelial cancer.
TCRs are often thought to be pre-clustered before T cell activation. Rossboth et al. use super-resolution microscopy and statistical image analysis to demonstrate that TCRs are in fact randomly distributed on resting T cells.
Lymphocytes interpret antigenic signals into a functional response. Richard et al. demonstrate that the overall qualitative response by CTLs is independent of TCR ligand strength; instead, ligands determine the rate and uniformity at which CTLs respond.
Foxo proteins are required for maintaining T cell quiescence. Turka and colleagues use a constitutively active Foxo1 in Treg cells to show that its downregulation is essential for maintaining their fitness in a competitive environment.
B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.
Regulatory factor X (RFX) is a transcription factor family comprising seven known members, yet the functional roles of RFX7 remain unknown. Guarda and colleagues show that RFX7 regulates natural killer (NK) cell survival and activity by limiting their cellular metabolism.
Tussiwand and colleagues show that pDCs develop predominantly from IL-7R+ lymphoid progenitor cells and that mature pDCs are transcriptionally and functionally heterogenous, on the basis of their lymphoid or myeloid lineage.
Typhoidal Salmonella is a major pathogen, but there is still a lack of knowledge about suitable vaccine antigens. Cerundolo and colleagues deep-phenotype bacteria-specific CD4+ T cells of Salmonella-infected volunteers to define cross-reactive and serovar-specific responses.
Liu and colleagues show that the ubiquitin E3 ligases Itch and WWP2 act together in regulating the strength of the TCR signal and differentiation toward the TH2 lineage.
The cytokines IL-17A and IL-17F bind via same receptor. Iwakura and colleagues demonstrate different functions for IL-17A and IL-17F in the gut, with the latter altering the production of antimicrobial peptides with consequent effects on the microbiota, the induction of Treg cells and immune-system homeostasis.
TIGIT is a co-inhibitory receptor associated with T cell exhaustion. Tian and colleagues demonstrate that TIGIT is the predominant inhibitory receptor on NK cells in both humans and mice and that its blockade enhances NK cell–dependent rejection of tumors in experimental models.
TCR signaling initiates a signaling cascade involving the kinases Lck and Zap70 and the adaptor LAT. Weiss and colleagues discover a proline-rich motif in LAT, which facilitates interactions among Lck, LAT and Zap70 for efficient TCR signaling.
Sixt, Stein and colleagues show that during T cell migration within lymphatic organs, the chemokine receptor CCR7 quantitatively controls the speed of a continuous actin flow, which is coupled to the environment by the integrin LFA-1.
CARD9 serves as an adaptor for C-type lectin receptor signaling. Xin Lin and colleagues show that CARD9 inhibits RelB-mediated IL-5 expression. The CARD9S12N mutant, prevalent in humans, cannot interact with RelB and promotes enhanced allergic responses to fungal pathogens.
Semaphorins play well-known roles in axon guidance. Kumanogoh and colleagues demonstrate that Semaphorin 6D cell-intrinsically activates anti-inflammatory macrophage polarization.
Carbohydrate-specific antibodies are typically thought to be of low affinity and produced by T cell–independent pathways. Wardemann and colleagues identify human memory B cells that can produce specific ‘affinity-matured’ antibodies to the O antigen of Klebsiella lipopolysaccharides.
McGaha and colleagues show that phagocytosis of apoptotic cells leads to activation of the transcription factor AhR and production of the cytokine IL-10 in phagocytes, in a manner dependent on the recognition of DNA.