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<p>γδ T cells represent a distinct subset of immune cells that play pivotal roles in maintaining cutaneous immune homeostasis and regulating inflammatory responses. Accumulating evidence has established neuro–immune interactions as critical modulators of skin inflammation and allergic reactions, with γδ T cells emerging as a key cellular link between the nervous and immune systems. This review summarizes recent advances in our understanding of how γδ T cells coordinate neuroimmune crosstalk in inflammatory and allergic skin diseases. γδ T cells are characterized by rapid effector responses and pronounced functional heterogeneity, enabling them to sense neuronal cues and, in turn, modulate sensory neuron activity. Through the production of cytokines such as IL-17, IL-22 and IL-3, γδ T cells influence neuronal excitability, neuropeptide release, and itch transmission, thereby shaping both inflammatory intensity and sensory outcomes. Conversely, subsets of γδ T cells express receptors for neurotransmitters, allowing them to directly respond to signals derived from sensory neurons. This bidirectional communication positions γδ T cells as critical regulators linking neural sensing to innate and adaptive immune responses in the skin. Furthermore, we discuss the current blind spots in γδ T cell–related neuro–immune research, as well as potential perspectives and future directions for the field. A deeper understanding of γδ T cell subset specialization, neuron–immune coupling specificity, and tissue-context–dependent regulation will be essential for translating these insights into precise interventions for inflammatory and allergic skin disorders.&#xa0;</p>

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γδ T Cell-Mediated Neuroimmune Interactions in Skin Inflammation and Allergy

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Shixiong Peng,
  • Tetsuya Honda

摘要

γδ T cells represent a distinct subset of immune cells that play pivotal roles in maintaining cutaneous immune homeostasis and regulating inflammatory responses. Accumulating evidence has established neuro–immune interactions as critical modulators of skin inflammation and allergic reactions, with γδ T cells emerging as a key cellular link between the nervous and immune systems. This review summarizes recent advances in our understanding of how γδ T cells coordinate neuroimmune crosstalk in inflammatory and allergic skin diseases. γδ T cells are characterized by rapid effector responses and pronounced functional heterogeneity, enabling them to sense neuronal cues and, in turn, modulate sensory neuron activity. Through the production of cytokines such as IL-17, IL-22 and IL-3, γδ T cells influence neuronal excitability, neuropeptide release, and itch transmission, thereby shaping both inflammatory intensity and sensory outcomes. Conversely, subsets of γδ T cells express receptors for neurotransmitters, allowing them to directly respond to signals derived from sensory neurons. This bidirectional communication positions γδ T cells as critical regulators linking neural sensing to innate and adaptive immune responses in the skin. Furthermore, we discuss the current blind spots in γδ T cell–related neuro–immune research, as well as potential perspectives and future directions for the field. A deeper understanding of γδ T cell subset specialization, neuron–immune coupling specificity, and tissue-context–dependent regulation will be essential for translating these insights into precise interventions for inflammatory and allergic skin disorders.