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CCL20, γδ T cells, and IL‐22 in corneal epithelial healing
Author(s) -
Li Zhijie,
Burns Alan R.,
Miller Sarah Byeseda,
Smith C. Wayne
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-184804
Subject(s) - ccl20 , wound healing , cxcl1 , corneal epithelium , stromal cell , inflammation , interleukin 17 , t cell , chemistry , immunology , microbiology and biotechnology , epithelium , biology , immune system , chemokine , pathology , medicine , cancer research , chemokine receptor
After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6+ IL‐17+ γδ T cells migrate into the epithelium. γδ T‐cell‐deficient (TCRδ –/– ) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mRNA increased 19‐fold at 3 h, and protein increased ~ 16‐fold at 6 h after injury. Systemic or topical treatment of wild‐type C57BL/6 mice with anti‐CCL20 reduced γδ T‐cell accumulation in the cornea by >50% with a concomitant decrease in epithelial healing and stromal inflammation. In addition to CCR6 and IL‐17, corneal γδ T cells stained positively for RORγt, IL‐23R, and IL‐22. Anti‐IL‐22 reduced peak cell division of the healing epithelium by 52%. Treatment of TCRδ –/– mice with rIL‐22 significantly promoted wound closure, with peak epithelial cell division increased > 3‐fold. In addition, rIL‐22 restored neutrophil and platelet influx in the TCRδ –/– mice to wild‐type levels and increased CXCL1 production by wounded corneal explants > 2‐fold. These results indicate that an important aspect of the healing response to corneal epithelial abrasion includes CCL20‐dependent influx of CCR6+ IL‐17+ IL‐22+ γδ T cells and that IL‐22 contributes to the inflammatory response and promotes epithelial healing.—Li, Z., Burns, A. R., Byeseda Miller, S., Smith, C. W. CCL20, γδ T cells, and IL‐22 in corneal epithelial healing. FASEB J. 25, 2659–2668 (2011). www.fasebj.org