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TRPV1+ Neurons are Required for Antigen‐Specific Immune Responses
Author(s) -
BravoIñiguez Carlos,
Tynan Aisling,
Tracey Kevin,
Chavan Sangeeta
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02217
Subject(s) - trpv1 , nociceptor , transient receptor potential channel , chemistry , antigen , immune system , receptor , ovalbumin , microbiology and biotechnology , immunology , nociception , biology , biochemistry
The lung is densely innervated by sensory neurons expressing nociceptors including transient receptor potential vanilloid channel 1 (TRPV1 + ). Nociceptors detect and respond to pathogen‐associated molecular patterns and other inflammatory mediators. However, the function of nociceptors in regulating lung antigen‐specific immune responses is unknown. Here, using chemogenetic mice we reveal sensory nociceptor fibers expressing TRPV1 + are required for efficient antigen‐specific immune responses. Chemogenetics enable temporal control of neuron activity using Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Inhibitory G protein (Gi‐DREADD) is a modified muscarinic acetylcholine receptor that binds the ligand, clozapine‐N‐oxide (CNO), which triggers inhibitory G protein signaling to inhibit neuronal excitability. To selectively silence TRPV1 + nociceptors, we generated TRPV1‐Gi‐DREADD mice to transiently inhibit neuronal activity specifically in TRPV1 + neurons. CNO or Vehicle was administered intraperitoneally to TRPV1‐Gi‐DREADD mice 30 minutes prior to intratracheal immunization with 4‐Hydroxy‐3‐nitrophenylacetyl hapten coupled to ovalbumin (NP 27 ‐OVA). Chemogenetic inhibition of TRPV1 + neurons, before primary immunization, significantly diminishes NP‐specific antibody responses. We observe a significant reduction in NP‐specific IgG in mice receiving CNO as compared to vehicle controls at 14 days post‐immunization (Anti‐NP IgG 1 U/mL, Mean ± SEM, D14: vehicle, 120,877 ± 29,519, n=10 versus CNO, 42,525 ± 14,641, n=11, ** p=0.0017 ). These results indicate TRPV1+ sensory neurons are required to initiate primary antibody responses to novel antigens. These findings offer significant new insights into the biological mechanisms of vaccination.