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MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33
JM. Inclan-Rico, CM. Napuri, C. Lin, LY. Hung, AA. Ferguson, X. Liu, Q. Wu, CF. Pastore, A. Stephenson, UM. Femoe, F. Musaigwa, HL. Rossi, BD. Freedman, DR. Reed, T. Macháček, P. Horák, I. Abdus-Saboor, W. Luo, DR. Herbert
Language English Country United States
Document type Journal Article
Grant support
T32 AI007532-24
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
R01 AI164715-01
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
U01 AI163062-01
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
R01 AI123173-05
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
NLK
ProQuest Central
from 2000-07-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-07-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-07-01 to 1 year ago
- MeSH
- Dendritic Cells immunology MeSH
- Interleukin-33 * metabolism immunology MeSH
- Skin immunology parasitology MeSH
- Humans MeSH
- Macrophages immunology metabolism MeSH
- Myeloid Cells immunology metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Neurons immunology metabolism MeSH
- Pruritus immunology MeSH
- Receptors, G-Protein-Coupled * metabolism immunology genetics MeSH
- Schistosoma mansoni * immunology MeSH
- Schistosomiasis mansoni * immunology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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.
Department of Neuroscience School of Medicine University of Pennsylvania Philadelphia PA USA
Department of Parasitology Faculty of Science Charles University Prague Czech Republic
References provided by Crossref.org
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