Location: Children's Nutrition Research Center
Title: Icam-1 Is Necessary for Epithelial Recruitment of Gammadelta T Cells and Efficient Corneal Wound Healing. Authors
|Byeseda, Sarah -|
|Burns, Alan -|
|Dieffenbaugher, Sean -|
|Rumbaut, Rolando -|
|Smith, Wayne -|
|Li, Zhijie -|
Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 14, 2009
Publication Date: July 16, 2009
Citation: Byeseda, S.E., Burns, A.R., Dieffenbaugher, S., Rumbaut, R.E., Smith, W.C., Li, Z. 2009. ICAM-1 is necessary for epithelial recruitment of gammadelta T cells and efficient corneal wound healing. American Journal of Pathology. 175(2):571-579. Interpretive Summary: In earlier studies, we have shown that a specific type of lymphocyte, called gamma delta T cell, is important in activation of inflammation in fat tissue when mice are put on a high fat diet. The purpose of this study was to determine how these lymphocytes migrate into the body’s tissues. We demonstrate that this type of lymphocyte requires an adhesion molecule called ICAM-1 to migrate into inflamed tissue. This is important information since we have shown in earlier studies that ICAM-1 is increased in fat tissue in animals on a high fat diet. This new information is important in our efforts to find targets for therapeutic control of the inflammation of obesity.
Technical Abstract: Wound healing and inflammation are both significantly reduced in mice that lack gammadelta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gammadelta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epithelial gammadelta T cells at 24 hours after epithelial abrasion. ICAM-1(-/-) mice had 50.9% (P < 0.01) fewer gammadelta T cells resident in unwounded corneal epithelium, which failed to increase in response to epithelial abrasion. Anti-ICAM-1 blocking antibody in wild-type mice reduced epithelial gammadelta T cells to a number comparable to that of ICAM-1(-/-) mice, and mice deficient in lymphocyte function-associated antigen-1 (CD11a/CD18), a principal leukocyte receptor for ICAM-1, exhibited a 48% reduction (P < 0.01) in peak epithelial gammadelta T cells. Re-epithelialization and epithelial cell division were both significantly reduced (approximately 50% at 18 hours, P < 0.01) after abrasion in ICAM-1(-/-) mice versus wild-type, and at 96 hours, recovery of epithelial thickness was only 66% (P < 0.01) of wild-type. ICAM-1 expression by corneal epithelium in response to epithelial abrasion appears to be critical for accumulation of gammadelta T cells in the epithelium, and deficiency of ICAM-1 significantly delays wound healing. Since gammadelta T cells are necessary for efficient epithelial wound healing, ICAM-1 may contribute to wound healing by facilitating gammadelta T cell migration into the corneal epithelium.