Research Briefing

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  • Many immune cell subsets move in an amoeboid fashion and do not require strong adhesive interactions with their surrounding when moving through interstitial tissue spaces. In stark contrast, we show that mast cells critically depend on integrin-mediated adhesion and interactions with the extracellular matrix to enable slow migration and site-specific positioning in tissues.

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  • Regulatory T (Treg) cells respond to interferon-γ (IFNγ) during viral infection and polarize to a T helper (TH)1-like state. Such Treg cells possess effector functions, such as the production of IFNγ, yet remain stable and potently limit virus-specific effector T cell function, CD8+ T cell proliferation and the formation of central memory T cells.

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  • When an interstitial macrophage niche is empty, classical monocytes can proliferate locally in a manner that is restricted by the transcription factor MAFB, before undergoing differentiation into distinct macrophage subsets. These findings reveal a new function of monocytes and highlight the complex regulation of proliferation and differentiation during macrophage development.

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  • Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6+ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4+ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.

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  • The cholesterol metabolite receptor GPR183 regulates the secretion of IgA by intestinal plasma cells. This process requires epithelial cell sensing of commensal bacteria and the uptake of dietary cholesterol to generate the GPR183 ligand 7α,25-hydroxycholesterol. Upon GPR183 activation, IgA+ plasma cells remain at the center of intestinal villi and reduce their antibody secretion.

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  • Intrathymic dendritic cell (DC)-biased precursors act as hematopoietic stromal cells that support the generation of human T cell progenitors from hematopoietic progenitor cells, via crosstalk with immature thymocytes that express TNF receptor 2. This function of DC precursors can be exploited to generate T cell precursors and competent T cells for cell therapy.

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  • Exhausted effector T cells accumulate in tumors and are the intended targets of cancer immunotherapy. New data suggest that upon infiltration and subsequent exhaustion in the tumor microenvironment, these T cells can take on an immunosuppressive function — and work against the immune response to cancer.

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  • Sterol regulatory element-binding protein (SREBP) signaling regulates cellular lipid homeostasis. We discovered that SREBP signaling in B cells is crucial for antibody responses and the generation of germinal centers and B cell memory compartments in response to vaccination. These results provide mechanistic insights that couple sterol metabolism to the quality and longevity of humoral immunity.

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  • We isolated CD4+ T cell clones from healthcare workers infected with SARS-CoV-2 during the first COVID-19 wave and identified 21 epitopes across three viral proteins: spike, membrane and nucleoprotein. Focusing on spike protein, for seven of ten epitopes mutated in variants of concern, we found that T cell recognition was impaired.

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  • Cohousing pet-store mice with laboratory mice leads to the natural transfer of microbes and subsequent inflammation in laboratory mice. Lung group 2 innate lymphoid cells — rapid responders to airway allergens — are transiently inhibited by inflammatory signals, but their activity recovers once the active infection subsides.

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  • By combining single-cell mRNA sequencing and a genetic pulse–chase mouse model, we identified multiple subsets of mouse long-lived plasma cells and showed that these cells can originate from diverse developmental routes.

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  • A stage-specific enhancer augments Notch1 signaling from the early thymic progenitor (ETP) through double-negative thymocyte stages. Enhanced Notch1 activity is required for T cell lineage differentiation at the later end of this developmental interval, but Notch1 also suppresses precocious T lineage commitment in ETPs and promotes their expansion as multi-lineage progenitors.

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  • We identified the transmembrane protein CMTM4 as an essential component of the IL-17 receptor. CMTM4 is required for membrane expression of IL-17 receptor subunit C and activation of IL-17A pro-inflammatory signaling. Lack of CMTM4 largely protects mice from experimental psoriasis, which suggests that targeting CMTM4 might alleviate IL-17-mediated autoimmunity.

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  • Immunotherapeutic targeting of the surface glycoprotein CD19 has markedly improved outcomes in patients with relapsed and refractory B cell progenitor acute lymphoblastic leukemia. Genome-wide CRISPR–Cas9 screening identifies modulators of CD19 mRNA processing that affect the abundance of the surface protein in human B cell leukemia cells, with the potential to improve antigen-directed immunotherapy efficacy.

    Research Briefing
  • During T cell activation, tRNA-m1A ‘writers’ TRMT61A and TRMT6 are upregulated to modify a group of early tRNA species and promote efficient translation of certain pre-cell-cycling proteins, thus ensuring rapid T cell proliferation and a timely adaptive immune response.

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  • Through access to healthy donors’ bronchoalveolar lavage (BAL) samples cryopreserved before the COVID-19 pandemic, we discovered CD4+ and CD8+ T cells able to cross-recognize SARS-CoV-2 among the airway tissue-resident memory pool. Pre-pandemic donors with detectable SARS-CoV-2-cross-reactive T cells in their airways also had stronger immunity to human seasonal coronaviruses.

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  • Intestinal group 3 innate lymphoid (ILC3) cells exhibit increased mobility in response to flagellin-mediated inflammation. This ‘patrolling’ behavior promotes IL-22 diffusion and prevents intestinal epithelial cell death. Enhanced ILC3 dynamics rely on environmental cues and suggest a prominent ILC3 tissue adaptation that reinforces intestinal barrier integrity.

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  • Tissue-destructive fibroblasts in arthritis are driven by the transcription factor ETS1. Analysis of a cross-tissue, single-cell fibroblast dataset and genetic loss-of-function approaches further suggest that ETS1-expressing fibroblasts have a universal role in pathological tissue remodeling in multiple diseases, including arthritis, colitis and cancer.

    Research Briefing