European Journal of Immunology最新文献

Zinc finger E-box binding protein 2 (ZEB2) is a key factor in the differentiation of naïve CD8⁺ T cells into effector and memory T cells. However, the precise regulatory role of ZEB2 in cytotoxic CD8⁺ T cells remains unknown. Our recent DNA methylation analysis of cytomegalovirus (CMV)-specific human CD8⁺ T cells revealed two differentially methylated regions (DMRs) within the ZEB2 locus. In the present study, we show that these ZEB2 DMRs undergo pronounced demethylation during T cell differentiation. In particular, terminally differentiated CD8⁺ T cells and cytotoxic CD4⁺ T cells show an almost complete demethylation. Demethylation of the ZEB2 DMRs correlates strongly with ZEB2 expression in all T cell subsets. Furthermore, DNA methylation patterns remain stable during long-term in vitro culture. ZEB2 knockout in CD8⁺ effector T cells results in altered gene expression profiles, affecting genes related to cell–cell adhesion and impairing the cytotoxic capacity in CMV-specific killing assays. Our data show that ZEB2 expression contributes to the differentiation of naïve CD8⁺ T cells into effector and memory T cells and regulates the functional properties of virus-specific cytotoxic CD8⁺ T cells.

“Chen Q, Zheng J, Wang D, Liu Q, Kang L, Gao X, Lin Z. Nitrosonisoldipine is a selective inhibitor of inflammatory caspases and protects against pyroptosis and related septic shock. Eur J Immunol. 2021; 51(5):1234-1245.”

In Figure 4B of this article, the upper photo of “+10 µM nigericin” is wrongly labeled; it should be “+ 5 mM ATP”, which is consistent with the figure legends and description in the main text. We also found that an image of “−” negative control group and an image of “+ 5 mM ATP” positive control group were incorrectly used. In addition, we moved the upper group of images to the lower panel in the corrected figure to match the statistical results. It does not affect our results. The correct figure and figure legend are as follows:

We apologize for this error.

Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.

In the almost two decades since their discovery, innate lymphoid cells (ILCs) have received considerable attention for their roles in immune defense and tissue repair. However, a growing body of evidence now highlights a broader functional spectrum, positioning ILCs as key integrators of environmental cues that support tissue-specific metabolic adaptation. These insights challenge traditional immune-centric paradigms, suggesting that ILCs also contribute to core physiological functions of tissues. In this review, we discuss emerging roles for ILCs in the regulation of energy homeostasis during adulthood, including nutrient sensing, uptake, storage, and utilization. We further examine how these functions may be shaped during the neonatal period, a critical window of developmental transitions that coincides with the establishment of ILC tissue residency. We suggest that ILCs may act as early regulators of postnatal metabolic adaptation, playing a fundamental role in the physiological maturation of tissues after birth.

“Zheng J, Wang D, Chen Q, Liu Q, Lin Z, Hu Q, Wu X, Gao X, Li Q, Ren J. Hypertonic saccharide solution delays pyroptosis in murine macrophages regardless of the membrane binding of gasdermin D N-terminal. Eur J Immunol. 2020;50(3):464–7.”

Supporting Information Figure S4. Hypertonic solution inhibits noncanonical pyroptosis in THP-1 cells. THP-1 cells electroporated with LPS were grown in normal media, hypertonic solution, or media containing 5 mM glycine. THP-1 cells electroporated without LPS are used as a negative control. (A) Percentage of LDH release at 1 h. (B) Representative bright-field images were taken 90 min after the electroporation. Arrowheads indicate representative pyroptotic cells. Bar = 50 µm. (C) Percentage of pyroptotic blebbing was counted. Data are shown as mean + SD and are representative of five independent experiments. Significance was calculated compared with THP-1 cells electroporated with LPS and grown in normal media. *p < 0.05, **p < 0.01 (two-tailed Student's t-test).

We apologize for this error.

Tolerogenic dendritic cells (tolDCs) that dampen T cell responses can be induced from blood monocytes in vitro using factors such as Vitamin D3 (VitD), dexamethasone, IL-10, or rapamycin. However, challenges remain in obtaining robust and efficient generation of cell therapy-based tolDCs without compromising their viability. We recently reported that CCR2-dependent recruitment of monocytic cells, with the capacity to dampen T-helper responses, occurs in mice treated with a single-stranded oligonucleotide (ssON). Here, we investigated the effects of this immunomodulatory noncoding ssON on differentiating human monocytes towards DC in the presence of IL-4 and GM-CSF (moDC). The moDC differentiated in the presence of ssON upregulated CD1a but also increased their expression of PD-L1. The differentiation of monocytes to moDC in the presence of ssON introduced transcriptomic changes, many of which overlapped with VitD-moDC and resulted in moDCs with altered lipopolysaccharide (LPS)-responsiveness. Moreover, ssON-moDC exhibited a low capacity to stimulate alloreactive T cells in vitro and instead promoted the induction of CD4⁺FoxP3⁺CD25⁺ T cells. Experiments using chemical reagents support a role for PPAR-γ in the generation of ssON-moDC. Collectively, our data show that monocytes differentiated with IL-4, GM-CSF, and ssON generate cells with phenotypic and functional characteristics of tolDCs.

Activating immune receptors provides mechanisms for phagocytes to elicit important effector functions that promote the killing of microbes. Leukocyte immunoglobulin-like receptor A5 (LILRA5), an orphan immune receptor expressed by human phagocytes and co-localising with FcRγ, remains poorly characterised. To address this, we developed a highly specific anti-LILRA5 monoclonal antibody that has agonistic properties. We show LILRA5 expression on naïve monocytes and neutrophils, and that ligation of LILRA5 stimulates ROS production. While increased LILRA5 transcripts have been associated with sepsis, we also observed increased levels in patients with systemic infection but without sepsis complications. Ex vivo bacterial infection of whole blood did not alter surface LILRA5 expression, but LPS stimulation changed expression levels, indicating that surface LILRA5 expression is dynamic and likely regulated post-transcriptionally, changing responses to different stimuli or over time. Soluble (s)LILRA5 was enhanced in sera from sepsis patients and in supernatants of monocytes that were LPS-stimulated, indicating that shedding of LILRA5 from cell surfaces or that expression of sLILRA5 isoforms provides a mechanism to regulate surface LILRA5 expression levels. Finally, we show that altered surface LILRA5 expression influences LILRA5-induced ROS production capacity. Thus, LILRA5 is a dynamically regulated activating receptor expressed on phagocytes that stimulates ROS production.

Natural killer (NK) cells can protect from tumor-transformed cells using a fine-tuned machinery of activating and inhibiting receptors. An important activating receptor is Fc gamma receptor IIIa (FcγRIIIA or CD16A), which can trigger antibody-dependent cellular cytotoxicity (ADCC) when recognizing antibody-opsonized target cells. One strategy to boost ADCC responses may be achieved by inhibiting activation-induced shedding of CD16A from the NK cell surface. However, previous preclinical studies have shown contrasting results regarding the effectiveness and limitations of this approach. Here, microchip-based live cell-imaging was used to assess the consequences of CD16A shedding inhibition on the dynamics of NK cell cytotoxicity. The bispecific innate cell engager acimtamig (AFM13) was superior to IgG1 monoclonal antibodies in ADCC and in increasing the fraction of cytotoxic NK cells and serial killers. Under conditions where CD16A shedding was inhibited, acimtamig still triggered ADCC; however, the ability to promote serial killing was reduced and associated with impaired NK cell detachment from target cells. These results demonstrate that CD16A shedding represents an intrinsic feature of NK cell biology that is critical to sustain the antitumoral cytotoxicity of NK cells. This has implications for CD16A engineering of NK cell products and their combination with CD16A-directed NK cell engagers.