"MrgprA3 neurons selectively control myeloid-derived cytokines for IL-17 dependent cutaneous immunity".

Autor:	Inclan-Rico JM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Napuri CM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Lin C; Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA., Hung LY; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Ferguson AA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Wu Q; Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Pastore CF; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Stephenson A; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Femoe UM; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Rossi HL; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Reed DR; Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA., Luo W; Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.; Institute for Regenerative Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Abdus-Saboor I; Department of Biological Sciences, Zuckerman Mind, Brain, Behavior Institute, Columbia University, New York, New York, USA., Herbert DR; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Nov 30. Date of Electronic Publication: 2023 Nov 30.
DOI:	10.21203/rs.3.rs-3644984/v1
Abstrakt:	Skin employs interdependent cellular networks to facilitate barrier integrity and host immunity through ill-defined mechanisms. This study demonstrates that manipulation of itch-sensing neurons bearing the Mas-related G protein-coupled receptor A3 (MrgprA3) drives IL-17+ γδ T cell expansion, epidermal thickening, and resistance to the human pathogen Schistosoma mansoni through mechanisms that require myeloid antigen presenting cells (APC). Activated MrgprA3 neurons instruct myeloid APCs to downregulate interleukin 33 (IL-33) and up-regulate TNFα partially through the neuropeptide calcitonin gene related peptide (CGRP). Strikingly, cell-intrinsic deletion of IL-33 in myeloid APC basally alters chromatin accessibility at inflammatory cytokine loci and promotes IL-17/23-dependent epidermal thickening, keratinocyte hyperplasia, and resistance to helminth infection. Our findings reveal a previously undescribed mechanism of intercellular cross-talk wherein "itch" neuron activation reshapes myeloid cytokine expression patterns to alter skin composition for cutaneous immunity against invasive pathogens. Competing Interests: Declaration of interests. Authors have no conflicts to declare.
Databáze:	MEDLINE
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