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Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism

2020; National Academy of Sciences; Volume: 117; Issue: 28 Linguagem: Inglês

10.1073/pnas.2003603117

1091-6490

Sarthak Gupta, Shuichiro Nakabo, Luz P. Blanco, Liam J. O’Neil, Gustaf Wigerblad, Rishi R. Goel, Pragnesh Mistry, Kan Jiang, Carmelo Carmona‐Rivera, Diana Chan, Xinghao Wang, Hege Lynum Pedersen, Manasi Gadkari, Katherine Howe, Faiza Naz, Stefania Dell’Orso, Sarfaraz Hasni, Caeden Dempsey, Ashley Buscetta, Pamela A. Frischmeyer‐Guerrerio, Paul Kruszka, Maximilian Muenke, Luis M. Franco, Hong‐Wei Sun, Mariana J. Kaplan,

Single-cell and spatial transcriptomics

Significance Despite clear differences in female and male immunity that may contribute to variations in response to infections and predisposition to cancer and autoimmunity, the exact mechanisms that drive this stark contrast remain insufficiently characterized. Neutrophils play essential roles in homeostasis and disease, but little is known about how sex differences modulate their phenotype and function. Using transcriptomic and functional approaches, we report that healthy young adult females have an activated/mature neutrophil profile characterized by enhanced type I IFN pathway activity, enhanced proinflammatory responses, and distinct bioenergetics. We further show that these differences are cell specific and likely driven by sex hormones. Modulation of these pathways in neutrophils may provide more individualized, sex-specific therapeutic options in a variety of disease states.