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Confocal whole-mount of mouse skin: L1CAM-stained sensory nerve fibers in white with avidin-labeled mast cells in green

Peripheral Neuroimmunology · Heidelberg

Mast cells are the body's neuroimmune sentinels.

We study how mast cells sense environmental and tissue cues and convert them into rapid, protective responses — the fast interface between the immune system and the nervous system.

Whole-mount mouse skin · nerves, L1CAM (white) · mast cells, avidin (green)

Sentinels, not soldiers

A proteomic atlas showed mast cells are molecularly distinct from classical innate immune cells — wired for neuroimmune communication at barrier surfaces.

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They shape behavior

Sensitized mice avoid antigen-containing food; mice lacking mast cells or IgE do not. Mast cells drive antigen-avoidance — direct support for the toxin hypothesis of allergy.

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Signal converters

Mast cells translate immune and tissue states into organ-specific neural responses — itch, pain, nausea, avoidance — redefining them as central regulators of physiology.

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Lab news

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23 Jun 2026repost
11 Jul 2025repost
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Immunity @cp-immunity.bsky.social
DOCK8 in T cells promotes Th17 and Treg cell functionality to restrain mucosal mast cells and limit susceptibility to oral anaphylaxis
This paper by Janssen et al. shows that T cell-intrinsic DOCK8 expression is required to restrain mucosal mast cell expansion and prevent susceptibility to oral anaphylaxis. Mechanistically, DOCK8 deficiency causes a loss of intestinal Th17 cells, leading to microbial dysbiosis and elevated IL-25 production, which drives IL-4 secretion by Th2 cells to expand mucosal mast cells and increase intestinal permeability. This pathogenic cascade is left unrestrained because DOCK8-deficient regulatory T cells concurrently fail to suppress the intestinal IL-4 production and mast cell expansion.
19 May 2026repost
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Immunity @cp-immunity.bsky.social

Online now: Interleukin-4-producing type 2 innate lymphoid cells in the lymph node promote proallergic Tfh13 cell differentiation

Interleukin-4-producing type 2 innate lymphoid cells in the lymph node promote proallergic Tfh13 cell differentiation
This paper by Lee et al. demonstrates that lymph node-resident ILC2s selectively drive the differentiation of proallergic Tfh13 cells, which are required for high-affinity anaphylactic IgE responses. Mechanistically, ILC2s traffic into draining lymph nodes in a CCR8-dependent manner and produce IL-4, providing a specialized molecular signal necessary for the induction of pathogenic Tfh13 cells but dispensable for conventional Tfh2 cells.
13 May 2026repost
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Cell Reports @cp-cellreports.bsky.social

Vip+ vagal neurons control allergen-induced responses

Vip+ vagal neurons control allergen-induced responses
This paper by Zhu et al. identifies Vip+ vagal sensory neurons as a distinct subset necessary and sufficient for allergen-induced airway hyperreactivity and type 2 cytokine expression in the lung. Mechanistically, these neurons relay peripheral lung allergen signals to the nucleus of the solitary tract (nTS) in the brainstem and drive asthmatic pathology via NGFR signaling, defining a specific body-brain neuroimmune axis in asthma.
06 May 2026repost
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Waggoner Lab @labwaggoner.bsky.social

Review @annualreviews.bsky.social
The Neuroimmune Circuitry of Peripheral Sensory Neuron Subtypes in Chronic Pain
www.annualreviews.org/content/jour...

This review by Yong and Renthal highlights how distinct peripheral sensory neuron subtypes, identified via single-cell transcriptomics, form context-specific neuroimmune circuits to coordinate tissue repair and immune responses. They detail how the dysregulation of these subtype-specific interactions contributes to neuroinflammatory diseases, including atopic dermatitis, headache, and neuropathic pain, presenting these circuits as precise therapeutic targets.
27 Mar 2026repost
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Immunity @cp-immunity.bsky.social

Online now: Tuft cells promote reactivation of memory Th2 cells and are required for protective immunity to intestinal helminth re-infection

Tuft cells promote reactivation of memory Th2 cells and are required for protective immunity to intestinal helminth re-infection
This paper by Stanbery et al. demonstrates that intestinal tuft cells are essential for protective immunity against secondary Heligmosomoides polygyrus bakeri infection by releasing IL-25 and LTC4 to reactivate memory Th2 cells. These tissue-specific cues drive Th2 cell production of IL-13, which acts in tandem with granuloma formation to mediate effective worm expulsion from the intestinal lumen.
10 Mar 2026repost
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Nature Reviews Immunology @natrevimmunol.nature.com

Early life allergen sensitivity starts in the skin

Early life allergen sensitivity starts in the skin
This research highlight by Bird summarizes a study by Xing et al. showing that a post-natal window of hypothalamic-pituitary-adrenal axis immaturity results in low glucocorticoid levels, allowing dermal cDC2s to act as "peripheral immune inducers" that directly trigger acute type 17 skin inflammation in response to allergens. This localized dermal inflammation drives helper T 2 cell sensitization in draining lymph nodes, establishing enhanced susceptibility to subsequent systemic and respiratory allergic challenges.
09 Mar 2026repost
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Mucosal Immunology @mucosalimmunol.bsky.social

Interaction between airway basal cells, mast cells and type 2 immunity contributes to epithelial barrier dysfunction in allergic rhinitis: www.mucosalimmunology.org/article/S193...

This paper by Ruysseveldt et al. establishes a bidirectional proinflammatory axis between nasal basal cells and mast cells that drives epithelial barrier dysfunction in allergic rhinitis. They demonstrate that Der p1 acts via PAR2 to trigger basal cell release of cytokines and chemokines, including SCF, which recruits mast cells to the epithelium. In turn, mast cell-derived histamine and tryptase stimulate further basal cell chemokine release, while histamine combined with IL-4 and IL-13 directly impairs basal cell proliferation, mobility, differentiation, and barrier formation.
01 Mar 2026paperrepost
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Nature @nature.com

The most influential explanation of a recent surge in allergies is the hygiene hypothesis

go.nature.com/40woBkB

Environmental exposure trains the immune system to dampen allergic responses
This commentary by Chatila highlights a study by Erickson et al. demonstrating that exposure to microbe-rich environments (such as pet-shop housing) drives environmental immune imprinting that closes the early-life window of allergy susceptibility. This protection is mediated by two distinct pathways: a history of pathogen exposure that primes a broad, highly cross-reactive IgG-mediated type 1 immunity capable of intercepting unfamiliar allergens, and a non-inflammatory oral tolerance pathway where dietary exposures generate cross-protective, regulatory T cell-mediated resistance to antigenically related foods.
25 Feb 2026repost
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Immunity @cp-immunity.bsky.social

Online now: Sensory neuron production of substance P and TAFA4 promotes disease tolerance during viral infection

Sensory neuron production of substance P and TAFA4 promotes disease tolerance during viral infection
This paper by Roger et al. demonstrates that herpes simplex virus type 1 directly activates sensory neurons to release substance P and TAFA4, which independently promote disease tolerance by limiting immunopathology without altering viral clearance. In the skin, TRPV1+ neuron-derived substance P restricts neutrophil infiltration via MRGPRA1 to accelerate healing, while in the dorsal root ganglia, a TAFA4-IL10 axis acts post-viral clearance to resolve inflammation.
20 Feb 2026repost
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Immunity @cp-immunity.bsky.social

Online now: Hyperactivation of sympathetic nerves fuels basophil infiltration in atopic dermatitis

Hyperactivation of sympathetic nerves fuels basophil infiltration in atopic dermatitis
This paper by Xie et al. identifies a sympathetic nervous system-basophil axis where atopic dermatitis-induced anxiety hyperactivates skin sympathetic neurons, releasing norepinephrine to stimulate beta2-adrenergic receptors on basophils. This signaling enhances basophil motility and activates the CCL6-CCR1 chemokine pathway (CCL23-CCR1 in humans), fueling basophil infiltration and amplifying chronic skin inflammation.
07 Jan 2026paperrepost
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Nature @nature.com

Nature research paper: Neuro-epithelial circuits promote sensory convergence and intestinal immunity

go.nature.com/4qeRjlt

Neuro-epithelial circuits promote sensory convergence and intestinal immunity - Nature
This paper by Zhang et al. demonstrates that TRPV1+ pain-sensing nociceptors cooperate with chemosensory epithelial tuft cells via CGRP signaling to drive intestinal type 2 inflammation and anti-helminth immunity, showing that nociceptor activation promotes epithelial progenitor proliferation and that epithelial/tuft cell-intrinsic CGRP receptors are required for this tissue adaptation.
04 Jan 2026repost
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Cell Reports @cp-cellreports.bsky.social

Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation

Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation
This paper by Nagai et al. identifies mast cell-intrinsic CysLT2R as a checkpoint molecule that inhibits CysLT1R-mediated mast cell activation and dust mite-induced type 2 lung inflammation by leveraging G-beta-gamma-dependent adenylate cyclase potentiation to enhance cAMP/PKA signaling.
03 Jan 2026repost
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Waggoner Lab @labwaggoner.bsky.social

Review @jci.org
Mechanisms and clinical implications of gut-brain interactions
www.jci.org/articles/vie...

This review by Lorsch and Liddle details the specific mechanisms of gut-brain communication—including the enteroendocrine-neural circuit and neuroimmunological pathways—and shows how these connections drive clinical disease and can be therapeutically leveraged by agents like GLP-1 receptor agonists.
01 Jan 2026repost
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Science Magazine @science.org

Humans may be genetically programmed to produce antibodies against peanut, suggests a #ScienceTranslationalMedicine study showing nonallergic people harbor convergent, germline-encoded antibodies against the allergen Ara h 2. https://scim.ag/3LqfEp9

Germline-encoded recognition of peanut underlies development of convergent antibodies in humans
This paper by Marini-Rapoport et al. reveals that human IgG recognition of the immunodominant peanut allergen Ara h 2 is intrinsically programmed by the germline antibody repertoire, driven by structural convergence across diverse, highly prevalent gene rearrangements that target a common public epitope in both allergic and non-allergic individuals.
03 Dec 2025repost
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Science Magazine @science.org

This paper by Conde et al. demonstrates that a conjugate vaccine coupling a mutated human IgE fragment to a CRM carrier induces durable, neutralizing anti-IgE autoantibodies in humanized mice, providing long-term protection against systemic and cutaneous anaphylaxis without compromising anti-helminth immunity. #ScienceTranslationalMedicine. https://scim.ag/3XxHAdi

24 Jul 2025paperrepost
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Jonathan Kipnis @jonykipnis.bsky.social

Excited to share our new work, led by an exceptional graduate student, Tornike Mamuladze, on the role of meningeal mast cells in regulation of brain/dura access points, with implications to CSF flow dynamics and meningitis || www.cell.com/cell/fulltex...

Mast cells regulate the brain-dura interface and CSF dynamics
This paper by Mamuladze et al. reveals that dural mast cells regulate cerebrospinal fluid (CSF) dynamics at arachnoid cuff exit (ACE) points, where degranulation-induced histamine release dilates bridging veins to restrict CSF flow, thereby recruiting neutrophils and forming a critical barrier that prevents pathogens from spreading into the brain during meningitis.
25 Jun 2025repost
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Immunity @cp-immunity.bsky.social

This paper by Janssen et al. demonstrates that DOCK8 deficiency drives food allergy and oral anaphylaxis by disrupting T regulatory cell and Th17 function, causing dysbiosis and an IL-25/IL-4 cascade that expands mucosal mast cells and increases intestinal permeability.

DOCK8 in T cells promotes Th17 and Treg cell functionality to restrain mucosal mast cells and limit susceptibility to oral anaphylaxis
04 May 2025repost
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Immunity @cp-immunity.bsky.social

This review by Brian Kim and David Artis details how peripheral sensory neuroimmunology has emerged as a distinct field by revealing critical interactions between the immune and sensory nervous systems that govern allergy, infection, autoimmunity, and tissue homeostasis.

The sensory neuroimmune frontier
29 Jan 2026repost
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Neuron @cp-neuron.bsky.social

This review by Kothari and Dong outlines how bidirectional neuroimmune crosstalk—where immune signaling molecules directly activate sensory neurons and neuropeptides modulate local immune responses—drives pathologic itch, highlighting tissue-specific mechanisms and novel targetable pathways for pruritic diseases.

The neuroimmune axis: Integrating two systems to decipher itch