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Antibody responses to immunization require sensory neurons

Aisling Tynan, Téa Tsaava, Manojkumar Gunasekaran, Isabel Snee, Tak W. Mak, Peder Olofsson, View ORCID ProfileUlf Andersson, Sangeeta S. Chavan, Kevin J. Tracey
doi: https://doi.org/10.1101/860395
Aisling Tynan
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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Téa Tsaava
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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Manojkumar Gunasekaran
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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Isabel Snee
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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Tak W. Mak
The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
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Peder Olofsson
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USALaboratory of Immunobiology, Center for Bioelectronic Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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Ulf Andersson
Department of Women’s and Children’s Health, Karolinska Institute, Karolinska University Hospital, 17176 Stockholm, Sweden
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  • ORCID record for Ulf Andersson
Sangeeta S. Chavan
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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  • For correspondence: schavan@northwell.edu KJTracey@northwell.edu
Kevin J. Tracey
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA
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  • For correspondence: schavan@northwell.edu KJTracey@northwell.edu
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Abstract

Mammals store memories in the nervous and immune systems. Sensory neurons have been implicated in enhancing neurological memory, but whether neurons participate during immunity to novel antigens is unknown. Here, mice rendered deficient in transient receptor potential vanilloid 1 (TRPV1)-expressing sensory neurons, termed “nociceptors,” fail to develop competent antibody responses to KLH and hapten-NP. Moreover, selective optogenetic stimulation of TRPV1 neurons during immunization significantly enhanced antibody responses to antigens. Thus, TRPV1 nociceptors mediate antibody responses to novel antigen, and stimulating TRPV1 nociceptors enhances antibody responses during immunization. This is the first genetic and selective functional evidence that nociceptors are required during immunization to produce antigen-specific antibodies.

Summary The first genetic and selective functional evidence showing that TRPV1-expressing nociceptors are required for competent antibody responses to novel antigen, and stimulating TRPV1 nociceptors enhances antibody responses to novel antigen.

  • Abbreviations

    TRPV1
    Transient Receptor Potenial Vanilloid 1
    KLH
    Keyhole limpet hemocyanin
    NP
    4-Hydroxy-3-nitrophenylacetyl hapten
    fMRI
    Functional Magnetic Resonance Imaging
    CGRP
    Calcitonin Gene-related peptide
    ELISA
    Enzyme-Linked Immunosorbent Assay
    Ig
    Immunoglobulin
    DTA
    Diphtheria toxin fragment A
    ChR2
    Channelrhodopsin-2
    PBS
    Phosphate Buffered Saline
    OVA
    Ovalbumin
    BSA
    Bovine Serum Albumin
    EDTA
    Ethylenediaminetetraacetic acid
    NEAA
    Non-essential Amino Acids
    FBS
    Fetal Bovine Serum
    LPS
    Lipopolysaccharide
    ELISpot
    Enzyme-linked Immunosorbent Spot
    LED
    Light-Emitting Diode
    ANOVA
    Analysis of Variance
    TCRβ
    T Cell Receptor Beta
    ASC
    Antibody Secreting Cell
    Hz
    Hertz
    DC
    Duty Cycle
  • Copyright 
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    Posted November 30, 2019.
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    Antibody responses to immunization require sensory neurons
    Aisling Tynan, Téa Tsaava, Manojkumar Gunasekaran, Isabel Snee, Tak W. Mak, Peder Olofsson, Ulf Andersson, Sangeeta S. Chavan, Kevin J. Tracey
    bioRxiv 860395; doi: https://doi.org/10.1101/860395
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    Antibody responses to immunization require sensory neurons
    Aisling Tynan, Téa Tsaava, Manojkumar Gunasekaran, Isabel Snee, Tak W. Mak, Peder Olofsson, Ulf Andersson, Sangeeta S. Chavan, Kevin J. Tracey
    bioRxiv 860395; doi: https://doi.org/10.1101/860395

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