降钙素基因相关肽
结膜
免疫学
胸腺基质淋巴细胞生成素
免疫系统
生物
先天性淋巴细胞
神经肽
医学
病理
先天免疫系统
受体
生物化学
作者
Mikiko Okano,Kiyoshi Hirahara,Masahiro Kiuchi,Miki Onoue,Chiaki Iwamura,Kota Kokubo,Takahisa Hishiya,Yuki Morimoto,Yuzuru Ikehara,Akira Murakami,Nobuyuki Ebihara,Masahiro Kiuchi
出处
期刊:Immunity
[Elsevier]
日期:2022-12-01
卷期号:55 (12): 2352-2368.e7
被引量:12
标识
DOI:10.1016/j.immuni.2022.09.016
摘要
Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunctiva, but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identified a subset of memory-type pathogenic Th2 cells that preferentially expressed Il1rl1-encoding ST2 and Calca-encoding calcitonin-gene-related peptide (CGRP) in the inflammatory conjunctiva using a single-cell analysis. The IL-33-ST2 axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. Pharmacological blockade and genetic deletion of CGRP signaling in vivo attenuated scratching behavior. The analysis of giant papillae from patients with severe allergic conjunctivitis revealed ectopic lymphoid structure formation with the accumulation of IL-33-producing epithelial cells and CGRP-producing pathogenic CD4+ T cells accompanied by peripheral nerve elongation. Thus, the IL-33-ST2-CGRP axis directs severe itch with neuro-reconstruction in the inflammatory conjunctiva and is a potential therapeutic target for severe itch in allergic conjunctivitis.
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