Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction
IntroductionEvidence demonstrates that sensory neurons respond to pathogenic/allergic infiltration and mediate immune responses, forming an integral part of host defense that becomes hypersensitized during allergy. Our objective was to investigate how asthmatic induction alters the pulmonary neuroim...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518771/full |
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| author | Hayden McSwiggin Rui Wang Rubens Daniel Miserani Magalhães Fengli Zhu Taylor A. Doherty Wei Yan Wei Yan Nicholas Jendzjowsky Nicholas Jendzjowsky |
| author_facet | Hayden McSwiggin Rui Wang Rubens Daniel Miserani Magalhães Fengli Zhu Taylor A. Doherty Wei Yan Wei Yan Nicholas Jendzjowsky Nicholas Jendzjowsky |
| author_sort | Hayden McSwiggin |
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| description | IntroductionEvidence demonstrates that sensory neurons respond to pathogenic/allergic infiltration and mediate immune responses, forming an integral part of host defense that becomes hypersensitized during allergy. Our objective was to investigate how asthmatic induction alters the pulmonary neuroimmune transcriptome. We hypothesized that asthmatic induction would upregulate genes in the vagal ganglia (nodose/jugular ganglia), which would be associated with asthmatic immunity, and that these would be clustered, primarily in nodose neurons. Furthermore, lungs would increase transcripts associated with nerve activation, and these would be centered in neural and neuroendocrine-like cells.MethodsStandard RNA sequencing, single nucleus-RNA sequencing, and spatial RNA sequencing of vagal ganglia. Standard RNA-sequencing and spatial RNA-sequencing of lungs in naïve and mice that have undergone asthmatic induction with Alternaria alternata.ResultsBulk RNA-seq revealed that genes related to allergen sensing were increased in asthmatic ganglia nodose/jugular ganglia compared to control ganglia. These genes were associated with nodose clusters as shown by single-nucleus RNA sequencing, and a distinct caudal-to-rostral spatial arrangement was presented as delineated by spatial transcriptomics. The distinct clusters closely match previous identification of nodose neuron clusters. Correspondingly, the lung transcriptome was altered with asthmatic induction such that transcripts associated with neural excitation were upregulated. The spatial distribution of these transcripts was revealed by spatial transcriptomics to illustrate that these were expressed in neuroendocrine-like cells/club cells, and neurons.ConclusionsThese results show that the neuroimmune transcriptome is altered in response to asthmatic induction in a cell cluster and spatially distinct manner. |
| format | Article |
| id | doaj-art-9c6bcb47e6644fd18076db7815e71db2 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-9c6bcb47e6644fd18076db7815e71db22025-08-20T02:59:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15187711518771Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic inductionHayden McSwiggin0Rui Wang1Rubens Daniel Miserani Magalhães2Fengli Zhu3Taylor A. Doherty4Wei Yan5Wei Yan6Nicholas Jendzjowsky7Nicholas Jendzjowsky8The Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesDivision of Allergy and Immunology, Department of Medicine, University of California, San Diego, Veterans Affairs San Diego Healthcare System, La Jolla, CA, United StatesThe Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesDivision of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA, United StatesDivision of Respiratory and Critical Care Medicine and Physiology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, United StatesIntroductionEvidence demonstrates that sensory neurons respond to pathogenic/allergic infiltration and mediate immune responses, forming an integral part of host defense that becomes hypersensitized during allergy. Our objective was to investigate how asthmatic induction alters the pulmonary neuroimmune transcriptome. We hypothesized that asthmatic induction would upregulate genes in the vagal ganglia (nodose/jugular ganglia), which would be associated with asthmatic immunity, and that these would be clustered, primarily in nodose neurons. Furthermore, lungs would increase transcripts associated with nerve activation, and these would be centered in neural and neuroendocrine-like cells.MethodsStandard RNA sequencing, single nucleus-RNA sequencing, and spatial RNA sequencing of vagal ganglia. Standard RNA-sequencing and spatial RNA-sequencing of lungs in naïve and mice that have undergone asthmatic induction with Alternaria alternata.ResultsBulk RNA-seq revealed that genes related to allergen sensing were increased in asthmatic ganglia nodose/jugular ganglia compared to control ganglia. These genes were associated with nodose clusters as shown by single-nucleus RNA sequencing, and a distinct caudal-to-rostral spatial arrangement was presented as delineated by spatial transcriptomics. The distinct clusters closely match previous identification of nodose neuron clusters. Correspondingly, the lung transcriptome was altered with asthmatic induction such that transcripts associated with neural excitation were upregulated. The spatial distribution of these transcripts was revealed by spatial transcriptomics to illustrate that these were expressed in neuroendocrine-like cells/club cells, and neurons.ConclusionsThese results show that the neuroimmune transcriptome is altered in response to asthmatic induction in a cell cluster and spatially distinct manner.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518771/fullvagusasthmaAlternaria alternataRNA sequencingsingle-nucleus RNA sequencingspatial RNA sequencing |
| spellingShingle | Hayden McSwiggin Rui Wang Rubens Daniel Miserani Magalhães Fengli Zhu Taylor A. Doherty Wei Yan Wei Yan Nicholas Jendzjowsky Nicholas Jendzjowsky Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction Frontiers in Immunology vagus asthma Alternaria alternata RNA sequencing single-nucleus RNA sequencing spatial RNA sequencing |
| title | Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| title_full | Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| title_fullStr | Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| title_full_unstemmed | Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| title_short | Comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| title_sort | comprehensive sequencing of the lung neuroimmune landscape in response to asthmatic induction |
| topic | vagus asthma Alternaria alternata RNA sequencing single-nucleus RNA sequencing spatial RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1518771/full |
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