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The authors show that early Th2 cell differentiation is driven via prolonged T–DC macro-clustering in lymph nodes and occurs in a skin site-specific manner 
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A Blueprint for #Tumor-Infiltrating #Bcells across Human #Cancers | Breaking OPEN ACCESS Study Online Now at Science Magazine + Accompanying OPEN ACCESS…
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Today we celebrate the incredible advancements in immunology that help protect us from disease and pave the way for healthier futures.
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Have you ever wondered why, during the COVID-19 pandemic, the elderly were at greater risk for severe disease, often resulting in hospitalisations, ICU admissions and even death? And why did most children not show any symptoms, despite being infected with the same virus? Then, you’ll find this year’s theme for the International Day of Immunology particularly intriguing: ‘Immunity through the ages’.
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Day of Immunology Celebrate your amazing immune system on the 29 April by attending events around Australia and New Zealand. Established in 2005 by the European Federation of Immunological Societies (EFIS), the success of Day of Immunology led to it being celebrated worldwide since 2007.
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Editor’s summaryIn response to infection, a small protein called interferon-γ (IFN-γ) is synthesized and released by several types of cells belonging to the immune system. IFN-γ acts on both immune and nonimmune cells to provide protection against bacteria, parasites, and fungi. Casanova et al. review how advances in IFN-γ research and the study of conditions resulting from IFN-γ deficiencies have, together, improved understanding of host protection and specific contributions provided by IFN-γ. Moreover, the authors evaluate the prospects of using IFN-γ as a therapeutic agent for infectious disease. —Sarah H. Ross
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Abstract. Transplanted organs carry donor immune cells into the recipient, the majority of which are tissue-resident macrophages (TRMs). The role they play
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Plus de 30 ans après la dernière épidémie importante au Québec, la rougeole fait à nouveau les manchettes. Des chercheurs tentent de comprendre comment le virus réussit à anéantir l’immunité contre d’autres maladies.
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Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function1. To study these ‘kiss-and-run’ interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts)2, an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+ T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+ T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8+ T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell–cell interactions across multiple biological systems. A paper reports the development of a universal tool for studying cellular interactions in biological systems, and demonstrates its coupling with single-cell transcriptomics methods to provide insights into the biology of the interactions.
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This work reveals that human effector CD8 T cells not only mediate cytotoxicity but also promote tissue remodeling. The remodeling potential was demonstrat
Gilbert C FAURE's insight:
CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem cell–mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T cell population in skin and adipose tissue from patients undergoing abdominal wall or abdominoplasty surgery. These tissue-resident CD8 T cells showed a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T cell products.
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Abstract. The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a h
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T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, we observed extensive activation and “macro-clustering” of early Th2 cells with migratory type-2 dendritic cells (cDC2s), generating specialized Th2-promoting microenvironments. Macro-clustering was integrin-mediated and promoted localized cytokine exchange among T cells to reinforce differentiation, which contrasted the behavior during Th1 responses. Unexpectedly, formation of Th2 macro-clusters was dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 from different dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting prolonged T cell activation, macro-clustering, and cytokine sensing. Thus, the generation of dedicated Th2 priming microenvironments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner.