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Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.

Authors
 Wungrak Choi  ;  Yu Jeong Byun  ;  Eunae Jung  ;  Hyemi Noh  ;  Amir R. Hajrasouliha  ;  Zahra Sadrai  ;  Eunju Chang  ;  Joon H. Lee  ;  Hyung Keun Lee 
Citation
 JOURNAL OF LEUKOCYTE BIOLOGY, Vol.97(2) : 413-424, 2015 
Journal Title
 JOURNAL OF LEUKOCYTE BIOLOGY 
ISSN
 0741-5400 
Issue Date
2015
MeSH
Allografts ; Animals ; Biomimetic Materials/pharmacology* ; Chemokine CCL2/immunology ; Chemokine CCL3/immunology ; Chemokine CCL5/immunology ; Corneal Transplantation* ; Gene Expression Regulation/drug effects* ; Gene Expression Regulation/immunology ; Graft Survival/drug effects* ; Graft Survival/immunology ; Male ; Mice ; Receptors, Chemokine* ; Transforming Growth Factor beta/immunology
Keywords
transplantation
Abstract
Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-β was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-β is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.
Full Text
http://www.jleukbio.org/content/97/2/413.long
DOI
10.1189/jlb.5A0414-233RR
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Hae Mi(노혜미)
Byun, Yu Jeong(변유정)
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
Jeong, Eun Ae(정은애)
Choi, Wungrak(최웅락) ORCID logo https://orcid.org/0000-0002-3015-2502
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139401
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