Journal: Nature Immunology

Abbreviation

Nat Immunol

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Nature

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ISSN

1529-2908
1529-2916

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Publications1 - 10 of 38
  • Dynamics in protein translation sustaining T cell preparedness
    Item type: Journal Article
    Wolf, Tobias; Jin, Wenjie; Zoppi, Giada; et al. (2020)
    Nature Immunology
    In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells (https://www.immunomics.ch).
  • The development and function of lung-resident macrophages and dendritic cells
    Item type: Journal Article
    Kopf, Manfred; Schneider, Christoph; Nobs, Samuel P. (2014)
    Nature Immunology
  • Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation
    Item type: Journal Article
    Feng, Xiaogang; Andersson, Tilde; Flüchter, Pascal; et al. (2025)
    Nature Immunology
    The tuft cell-group 2 innate lymphoid cell (ILC2) circuit orchestrates rapid type 2 responses upon detecting microbially derived succinate and luminal helminths. Our findings delineate key mechanistic steps involving IP3R2 engagement and Ca2+ flux, governing interleukin-25 (IL-25) production by tuft cells triggered by succinate detection. While IL-17RB has a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Supraoptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.
  • Harnessing CD3 diversity to optimize CAR T cells
    Item type: Journal Article
    Cardenas, Rubi M. -H. Velasco; Brandl, Simon M.; Melendez, Ana Valeria; et al. (2023)
    Nature Immunology
    Current US Food and Drug Administration-approved chimeric antigen receptor (CAR) T cells harbor the T cell receptor (TCR)-derived zeta chain as an intracellular activation domain in addition to costimulatory domains. The functionality in a CAR format of the other chains of the TCR complex, namely CD3 delta, CD3 epsilon and CD3 gamma, instead of zeta, remains unknown. In the present study, we have systematically engineered new CD3 CARs, each containing only one of the CD3 intracellular domains. We found that CARs containing CD3 delta, CD3 epsilon or CD3 gamma cytoplasmic tails outperformed the conventional zeta CAR T cells in vivo. Transcriptomic and proteomic analysis revealed differences in activation potential, metabolism and stimulation-induced T cell dysfunctionality that mechanistically explain the enhanced anti-tumor performance. Furthermore, dimerization of the CARs improved their overall functionality. Using these CARs as minimalistic and synthetic surrogate TCRs, we have identified the phosphatase SHP-1 as a new interaction partner of CD3 delta that binds the CD3 delta-ITAM on phosphorylation of its C-terminal tyrosine. SHP-1 attenuates and restrains activation signals and might thus prevent exhaustion and dysfunction. These new insights into T cell activation could promote the rational redesign of synthetic antigen receptors to improve cancer immunotherapy.
  • Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19
    Item type: Journal Article
    Hanson, Aimee L.; Mulè, Matthew P.; Ruffieux, Hélène; et al. (2024)
    Nature Immunology
    Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1–3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.
  • Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
    Item type: Journal Article
    LeibundGut-Landmann, Salomé; Gross, Olaf; Robinson, Matthew J.; et al. (2007)
    Nature Immunology
  • Reply to: Apolipoprotein C3 induces inflammasome activation only in its delipidated form
    Item type: Other Journal Item
    Zewinger, Stephen; Reiser, Jochen; Jankowski, Vera; et al. (2023)
    Nature Immunology
  • The role of recruitment versus training in influenza-induced lasting changes to alveolar macrophage function
    Item type: Other Journal Item
    Iliakis, Chrysante S.; Kulikauskaite, Justina; Aegerter, Helena; et al. (2023)
    Nature Immunology
  • The co-inhibitory receptor TIGIT promotes tissue-protective functions in T cells
    Item type: Journal Article
    Panetti, Camilla; Daetwyler, Rahel; Moncsek, Anja; et al. (2025)
    Nature Immunology
    The co-inhibitory receptor TIGIT suppresses excessive immune responses in autoimmune conditions while also restraining antitumor immunity. In viral infections, TIGIT alone does not affect viral control but has been shown to limit tissue pathology. However, the underlying mechanisms are incompletely understood. Here we found TIGIT+ T cells to express not only an immunoregulatory gene signature but also a tissue repair gene signature. Specifically, after viral infection, TIGIT directly drives expression of the tissue growth factor amphiregulin (Areg), which is strongly reduced in the absence of TIGIT. We identified regulatory T (Treg) cells, but not CD8+ T cells, as the critical T cell subset mediating these tissue-protective effects. In Treg cells, TIGIT engagement after T cell antigen receptor stimulation induces the transcription factor Blimp-1, which then promotes Areg production and tissue repair. Thus, we uncovered a nonclassical function of the co-inhibitory receptor TIGIT, wherein it not only limits immune pathology by suppressing the immune response but also actively fosters tissue regeneration by inducing the tissue growth factor Areg in T cells.
  • Myeloid C-type lectins in innate immunity
    Item type: Journal Article
    Robinson, Matthew J.; Sancho, David; Slack, Emma; et al. (2006)
    Nature Immunology
Publications1 - 10 of 38