Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model.
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.
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Wungrak
W
Choi
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Yu Jeong
YJ
Byun
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Eunae
E
Jung
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Hyemi
H
Noh
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Amir R
AR
Hajrasouliha
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Zahra
Z
Sadrai
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Eunju
E
Chang
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea.
Joon H
JH
Lee
*Institute of Vision Research, Department of Ophthalmology, and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea; Kentucky Lions Eye Center, Department of Ophthalmology, University of Louisville, Louisville, Kentucky, USA; Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; and Myunggok Eye Research Institute, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, Korea shadik@yuhs.ac.
Hyung Keun
HK
Lee
D064591:Allografts; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D016039:Corneal Transplantation; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta / Q000276:immunology; D000097628:Chemokine Receptor D6
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6; C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse
transplantation