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oai:repisalud.isciii.es:20.500.12105/157812024-09-27T08:37:07Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Montaldo, Elisa author Lusito, Eleonora author Bianchessi, Valentina author Caronni, Nicoletta author Scala, Serena author Basso-Ricci, Luca author Cantaffa, Carla author Masserdotti, Alice author Barilaro, Mattia author Barresi, Simona author Genua, Marco author Vittoria, Francesco Maria author Barbiera, Giulia author Lazarevic, Dejan author Messina, Carlo author Xue, Elisabetta author Marktel, Sarah author Tresoldi, Cristina author Milani, Raffaella author Ronchi, Paola author Gattillo, Salvatore author Santoleri, Luca author Di Micco, Raffaella author Ditadi, Andrea author Belfiori, Giulio author Aleotti, Francesca author Naldini, Matteo Maria author Gentner, Bernhard author Gardiman, Elisa author Tamassia, Nicola author Cassatella, Marco Antonio author Hidalgo, Andres author Kwok, Immanuel author Ng, Lai Guan author Crippa, Stefano author Falconi, Massimo author Pettinella, Francesca author Scapini, Patrizia author Naldini, Luigi author Ciceri, Fabio author Aiuti, Alessandro author Ostuni, Renato author 2022-10 Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools. Nat Immunol. 2022 Oct;23(10):1470-1483 10.1038/s41590-022-01311-1 1529-2916 Nature immunology 36138183 http://hdl.handle.net/20.500.12105/15781 Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress.