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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
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
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
od 2000-07-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-07-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2024-01-01 do Před 1 rokem
- MeSH
- dendritické buňky imunologie MeSH
- interleukin 33 * metabolismus imunologie MeSH
- kůže imunologie parazitologie MeSH
- lidé MeSH
- makrofágy imunologie metabolismus MeSH
- myeloidní buňky imunologie metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony imunologie metabolismus MeSH
- pruritus imunologie MeSH
- receptory spřažené s G-proteiny * metabolismus imunologie genetika MeSH
- Schistosoma mansoni * imunologie MeSH
- schistosomiasis mansoni * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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
Citace poskytuje Crossref.org
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