IgE recall responses sustain allergic disease, but their anatomical regulation remains poorly understood. Villazala-Merino et al. identify Tfh cell-derived IL-4 microniches within germinal centers as an anatomical checkpoint that favors IgE recall responses in lymphoid organs while limiting their generation in the lung mucosa.

How cumulative environmental allergen exposures are encoded by peripheral sensory neurons to shape immune responsiveness is unclear. Zhu et al. show that protease allergens induce an mTORC1-dependent, metabolically trained state in sensory neurons that amplifies later neuroimmune responses to allergens and enables cross-sensitization to antigenically distinct allergens.

Accumulating evidence implicates sensory neurons in tumor progression, but signals linking nociceptive activity to impaired antitumor immunity remain unclear. In a recent issue of Cell, Ho et al. show that nociceptor activation impedes TLS assembly through CGRP, and cigarette smoke engages this neuroimmune axis, promoting tumor growth independently of mutagenic effects.

ILC2s engage in bidirectional neuroimmune crosstalk that shapes diverse physiological functions, yet whether ILC2-mediated serotonergic signaling affects asthma pathophysiology remains unexplored. Luo et al. show that ILC2-derived serotonin promotes type 2 immunity and activates vagal sensory neurons, contributing to airway hyperreactivity, lung inflammation, and cough hypersensitivity upon RSV infection. These findings reveal an ILC2-neuron crosstalk in asthma pathophysiology.

Bioelectronic technologies are being deployed to treat many inflammatory conditions using transcutaneous auricular nerve stimulation. Shibuya et al. employ viral tracing, chemogenetics, and optogenetics to unveil a sensory skin-lung vagal reflex that suppresses allergic airway inflammation. They identify the neuropeptide CGRPβ as a key mediator and provide a rationale for transcutaneous bioelectronic neuromodulation in asthma.

Nature Reviews Immunology, Published online: 23 June 2026; doi:10.1038/s41577-026-01325-yTwentieth-century immunology was shaped by questions of recognition, diversity, response and tolerance. The next era may be defined by a different class of questions: how immune activity is embedded in organ physiology, inter-organ homeostasis and human biology.

T follicular helper 13 (Tfh13) cells are required for anaphylactic IgE responses, yet how these cells arise is unclear. Lee et al. show that allergen sensitization drives CCR8-dependent trafficking of ILC2s to lymph nodes, where they provide early IL-4 signals that selectively promote Tfh13 cells, revealing differentiation requirements distinct from Tfh2 cells.

Zhu et al. show that Vip+ vagal sensory neurons control allergen-induced airway hyperreactivity and type 2 inflammation. NGFR signaling is required for Vip+-mediated airway hyperreactivity. Vip+ neurons relay peripheral allergen signals to the brainstem, defining a lung-brain neuroimmune circuit that contributes to asthma pathogenesis.

Lung diseases drive substantial hospitalization, but available therapies remain limited. In this Review, Talbot and colleagues highlight pulmonary neuroimmunology — the bidirectional crosstalk between...

Stanbery et al. show that ILC2s are largely dispensable, but tuft cells remain essential for helminth clearance during secondary infection. Tuft cells are not required for Th2 priming. Instead, tuft cell effectors directly activate memory Th2 cells in the small intestine, extending the paradigm that Th2 cells require tissue-specific cues.

Nature Reviews Immunology, Published online: 10 March 2026; doi:10.1038/s41577-026-01289-zEarly life exposure to allergens triggers a unique mode of dendritic cell activation in the skin, inducing local inflammation and priming systemic allergic responses to subsequent exposures in later life.

Clean living conditions that lessen exposure to microorganisms are linked to an increase in allergies. Mouse data reveal how the environment affects allergic immune responses.

Neuroimmune interactions shape host responses to infection, but the molecular role of sensory neurons during viral infection remains unclear. Roger et al. show that HSV-1-activated sensory neurons produce substance P and TAFA4, which act in a tissue-specific manner to modulate inflammation and promote disease tolerance without affecting viral clearance.

Emotional stress worsens atopic dermatitis and its overall burden, yet the underlying mechanisms remain unclear. Xie et al. reveal that anxiety amplifies atopic dermatitis through sympathetic nervous system activation. Sympathetic release of norepinephrine engages β2-adrenergic receptor signaling on basophils, which then release the chemokine CCL6 to drive basophil recruitment and exacerbate skin inflammation.

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Crosstalk between the nervous and immune systems is imperative to maintain homeostasis, and disruptions to this balance can drive pathology. In this review, Kothari and Dong discuss neuroimmune mechanisms that regulate itch, with an emphasis on pruritic diseases and therapies.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Nagai et al. reveal that mast cell CysLT2 receptor functions as a checkpoint receptor that restrains CysLT1 receptor-mediated mast cell activation through Gβγ-dependent cAMP/PKA signaling. This study uncovers a protective pathway in asthma and highlights the therapeutic promise of LTD4-based CysLT2 receptor-biased agonists.