小柯机器人

日本千叶大学医学院免疫学系Toshinori Nakayama和Kiyoshi Hirahara研究组合作发现，白细胞介素33激活的神经肽CGRP产生记忆Th2细胞与体感神经元协作诱发结膜瘙痒。2022年10月21日出版的《免疫》杂志发表了这项成果。

他们通过单细胞分析，在结膜炎中发现了一组记忆型致病Th2细胞，该细胞优先表达Il1rl1编码的ST2和calca编码的降钙素基因相关肽(CGRP)。记忆Th2细胞中IL-33-ST2轴控制外周感觉C纤维轴突伸长和严重瘙痒的诱导。体内CGRP信号通路的药理阻断和遗传缺失可减弱抓挠行为。对严重变应性结膜炎患者的巨大乳头进行分析，发现异位淋巴样结构形成，产生IL-33的上皮细胞和产生CGRP的致病CD4+ T细胞聚集，伴有周围神经伸长。因此，IL-33-ST2-CGRP轴在结膜炎的神经重建中指导严重瘙痒，是过敏性结膜炎严重瘙痒的潜在治疗靶点。

据悉，过敏性结膜炎是一种以结膜严重瘙痒为特征的慢性炎症性疾病，但神经免疫相互作用如何形成严重瘙痒的发病机制尚不清楚。

附：英文原文

Title: Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch

Author: Mikiko Okano, Kiyoshi Hirahara, Masahiro Kiuchi, Miki Onoue, Chiaki Iwamura, Kota Kokubo, Takahisa Hishiya, Yuki Morimoto, Yuzuru Ikehara, Akira Murakami, Nobuyuki Ebihara, Toshinori Nakayama

Issue&Volume: 2022-10-21

Abstract: Allergic conjunctivitis is a chronic inflammatory disease that is characterized bysevere itch in the conjunctiva, but how neuro-immune interactions shape the pathogenesisof severe itch remains unclear. We identified a subset of memory-type pathogenic Th2cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin-gene-related peptide (CGRP) in the inflammatory conjunctiva usinga single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonalelongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacologicalblockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients withsevere allergic conjunctivitis revealed ectopic lymphoid structure formation withthe accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenicCD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axisdirects severe itch with neuro-reconstruction in the inflammatory conjunctiva andis a potential therapeutic target for severe itch in allergic conjunctivitis.

DOI: 10.1016/j.immuni.2022.09.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00511-8

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