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Allergens TRP a swITCH to Initiate Type 2 Immunity
Charlotte E Cheadle1, Drew A Glencross1, Catherine M Hawrylowicz1
1Asthma UK Centre for Allergic Mechanisms in Asthma, School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, United Kingdom.
Immunity
|November 18, 2020
Summary
Protease allergens activate sensory neurons, releasing substance P. This substance P then guides specific immune cells to lymph nodes, initiating allergic type-2 immunity.
Area of Science:
- Immunology
- Neuroscience
- Dermatology
Background:
- Allergens trigger type-2 immunity, crucial for host defense but implicated in allergic diseases.
- The precise mechanisms initiating type-2 immune responses remain incompletely understood.
- Sensory neurons and their mediators are increasingly recognized for roles beyond pain perception.
Purpose of the Study:
- To investigate the role of sensory neurons in the initiation of allergen-induced type-2 immunity.
- To identify specific molecular pathways linking allergen exposure to immune cell activation and migration.
- To explore the function of substance P and CD301b+ dendritic cells in this process.
Main Methods:
- Utilized a mouse model of allergic sensitization.
- Investigated the activation of TRPV1+ sensory neurons upon allergen challenge.
- Measured substance P release and its effect on immune cell trafficking.
- Analyzed the migration of CD301b+ dendritic cells to draining lymph nodes.
Main Results:
- Protease allergens were found to activate cutaneous TRPV1+ sensory neurons.
- Activated neurons released substance P, a key neuropeptide.
- Substance P signaling was essential for the migration of Th2-skewing CD301b+ dendritic cells.
- This migration to lymph nodes was critical for initiating the type-2 immune response.
Conclusions:
- Cutaneous activation of TRPV1+ sensory neurons by protease allergens initiates type-2 immunity.
- Substance P release mediates the migration of Th2-skewing CD301b+ dendritic cells to lymph nodes.
- This neuro-immune crosstalk represents a novel pathway in allergic sensitization.
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