Journal
IMMUNITY
Volume 55, Issue 12, Pages 2352-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2022.09.016
Keywords
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Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) [26221305, JP19H05650, 20H03685, 17K08876, 18K07164, 19K16683, JP21H05120]
- Japan Agency for Medical Research and Development, AMED [JP20ek0410060, JP22ek0410092]
- AMED-PRIME, AMED [JP20gm6110005]
- AMED-CREST, AMED [JP20gm1210003]
- JST FOREST Project [JPMJFR200R]
- JST-Moonshot RD [JPMJMS2025]
- SENTAN project [JP19hm0102069h001]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- MSD Life Science Foundation
- Naito Foundation
- Takeda Science Foundation
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This study 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. The IL-33-ST2-CGRP axis in memory Th2 cells controlled the axonal elongation of the peripheral sensory C-fiber and the induction of severe itch. It suggests that this axis could be a potential therapeutic target for severe itch in allergic conjunctivitis.
Allergic conjunctivitis is a chronic inflammatory disease that is characterized by severe itch in the conjunc-tiva, but how neuro-immune interactions shape the pathogenesis of severe itch remains unclear. We identi-fied 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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