Location: Children's Nutrition Research CenterTitle: CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing Author
|Zhijie, Li - Children's Nutrition Research Center (CNRC)|
|Burns, Alan - Children's Nutrition Research Center (CNRC)|
|Byeseda, Sarah - Children's Nutrition Research Center (CNRC)|
|Smith, Wayne - Children's Nutrition Research Center (CNRC)|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/13/2011
Publication Date: 4/25/2011
Citation: Zhijie, L., Burns, A.R., Byeseda, S.M., Smith, W.C. 2011. CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing. Federation of American Societies for Experimental Biology Conference. 25: 1-10.
Interpretive Summary: This study attempts to increase our understanding of how white blood cells participate in inflammation. It is a basic study in our overall effort to analyze the mechanisms of inflammation in diet induced obesity. We show that a protein called CCL20 can attract a type of white blood cell called gamma delta T cells into tissue. We have found in earlier studies that this type of T cell is important in adipose tissue inflammation. Here we show that these cells have the ability to produce a protein called IL-22, and that this protein has the function of further stimulating inflammation but also promoting healing of injured tissue. Future studies will analyze if gamma delta T cells produce IL-22 in adipose tissue and if this protein contributes to progression or healing in the tissues.
Technical Abstract: After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) 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 gamma delta 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 gamma delta T cells stained positively for ROR't, IL-23R, and IL-22. Anti-IL-22 reduced peak cell division of the healing epithelium by 52%. Treatment of TCRd (-/-) 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 TCRd (-/-) 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(+) gamma delta T cells and that IL-22 contributes to the inflammatory response and promotes epithelial healing.