Jing Hua1, Yiping Jin1, Yihe Chen1, Takenori Inomata1, HyunSoo Lee1, Sunil K Chauhan1, Nicos A Petasis2, Charles N Serhan3, Reza Dana1. 1. Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States. 2. Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California, United States. 3. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Abstract
PURPOSE: To analyze the effect of a resolvin D1 (RvD1) analogue (RvD1a) on dendritic cell maturation, T-cell sensitization, and allograft rejection in corneal allotransplantation. METHODS: The receptor expression of RvD1 (ALX/FPR2) on bone marrow-derived dendritic cells (BMDC) was measured using quantitative real-time PCR. We determined BMDC maturation after treatment with RvD1a using ELISA to measure interleukin (IL)-12 protein expression and flow cytometry to assess the expression of CD40, major histocompatibility complex (MHC) II, CD80, and CD86. After corneal transplantation in BALB/c mice, we analyzed T-cell infiltration in the cornea and the draining lymph nodes using flow cytometry. The enzyme-linked immunospot (ELISPOT) assay was used to measure T-cell sensitization via the direct and indirect pathway. Angiogenesis and lymphangiogenesis in the cornea after transplantation were measured using immunohistochemistry. Graft opacity and survival were evaluated by slit lamp biomicroscopy. RESULTS: The receptor for RvD1, lipoxin A4/formyl peptide receptor 2 (ALX/FPR2), was expressed at a significantly lower level on immature than mature dendritic cells (DCs), and RvD1a reduced DC expression of MHC II, CD40, and IL-12 following lipopolysaccharide (LPS) stimulation. Using a murine model of corneal transplantation, RvD1a-treated hosts exhibited significantly reduced allosensitization as demonstrated by decreased frequencies of interferon-gamma-secreting T cells in the draining lymph nodes, and reduced T-cell infiltration into the grafts. Graft survival was significantly enhanced and angiogenesis at the graft site was suppressed in RvD1a-treated hosts compared with vehicle-treated hosts. CONCLUSIONS: These results suggest that RvD1 inhibits DC maturation and reduces alloimmune sensitization following transplantation, thereby establishing a novel connection between resolvin D1 and the regulation of DC-mediated, antigen-specific immunity. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: To analyze the effect of a resolvin D1 (RvD1) analogue (RvD1a) on dendritic cell maturation, T-cell sensitization, and allograft rejection in corneal allotransplantation. METHODS: The receptor expression of RvD1 (ALX/FPR2) on bone marrow-derived dendritic cells (BMDC) was measured using quantitative real-time PCR. We determined BMDC maturation after treatment with RvD1a using ELISA to measure interleukin (IL)-12 protein expression and flow cytometry to assess the expression of CD40, major histocompatibility complex (MHC) II, CD80, and CD86. After corneal transplantation in BALB/c mice, we analyzed T-cell infiltration in the cornea and the draining lymph nodes using flow cytometry. The enzyme-linked immunospot (ELISPOT) assay was used to measure T-cell sensitization via the direct and indirect pathway. Angiogenesis and lymphangiogenesis in the cornea after transplantation were measured using immunohistochemistry. Graft opacity and survival were evaluated by slit lamp biomicroscopy. RESULTS: The receptor for RvD1, lipoxin A4/formyl peptide receptor 2 (ALX/FPR2), was expressed at a significantly lower level on immature than mature dendritic cells (DCs), and RvD1a reduced DC expression of MHC II, CD40, and IL-12 following lipopolysaccharide (LPS) stimulation. Using a murine model of corneal transplantation, RvD1a-treated hosts exhibited significantly reduced allosensitization as demonstrated by decreased frequencies of interferon-gamma-secreting T cells in the draining lymph nodes, and reduced T-cell infiltration into the grafts. Graft survival was significantly enhanced and angiogenesis at the graft site was suppressed in RvD1a-treated hosts compared with vehicle-treated hosts. CONCLUSIONS: These results suggest that RvD1 inhibits DC maturation and reduces alloimmune sensitization following transplantation, thereby establishing a novel connection between resolvin D1 and the regulation of DC-mediated, antigen-specific immunity. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Yaohong Tan; Fernando Cruz-Guilloty; Carlos A Medina-Mendez; Nicholas J Cutrufello; Rosa E Martinez; Maitee Urbieta; David Wilson; Yiwen Li; Victor L Perez Journal: J Immunol Date: 2012-05-16 Impact factor: 5.422
Authors: Ji-Liang Gao; Aude Guillabert; Jinyue Hu; Yingying Le; Eneko Urizar; Eva Seligman; Kevin J Fang; Xiaoning Yuan; Virginie Imbault; David Communi; Ji Ming Wang; Marc Parmentier; Philip M Murphy; Isabelle Migeotte Journal: J Immunol Date: 2007-02-01 Impact factor: 5.422
Authors: Sadani N Cooray; Thomas Gobbetti; Trinidad Montero-Melendez; Simon McArthur; Dawn Thompson; Adrian J L Clark; Roderick J Flower; Mauro Perretti Journal: Proc Natl Acad Sci U S A Date: 2013-10-09 Impact factor: 11.205
Authors: Nandini Krishnamoorthy; Raja-Elie E Abdulnour; Katherine H Walker; Braden D Engstrom; Bruce D Levy Journal: Physiol Rev Date: 2018-07-01 Impact factor: 37.312
Authors: Sarah K Orr; Romain A Colas; Jesmond Dalli; Nan Chiang; Charles N Serhan Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-03-13 Impact factor: 5.464
Authors: Parker F Duffney; Megan L Falsetta; Ashley R Rackow; Thomas H Thatcher; Richard P Phipps; Patricia J Sime Journal: J Clin Invest Date: 2018-07-02 Impact factor: 14.808