MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33.

Autor: Inclan-Rico JM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Napuri CM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lin C; Monell Chemical Senses Center, Philadelphia, PA, USA., Hung LY; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ferguson AA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Liu X; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wu Q; Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Pastore CF; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Stephenson A; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Femoe UM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Musaigwa F; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rossi HL; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Freedman BD; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Reed DR; Monell Chemical Senses Center, Philadelphia, PA, USA., Macháček T; Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic., Horák P; Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic., Abdus-Saboor I; Department of Biological Sciences, Zuckerman Mind, Brain, Behavior Institute, Columbia University, New York, NY, USA., Luo W; Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Regenerative Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Herbert DR; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. debroski@vet.upenn.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Nov; Vol. 25 (11), pp. 2068-2084. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1038/s41590-024-01982-y
Abstrakt: Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17 + γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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