title: Expression of the chemokine decoy receptor D6 mediates dendritic cell function and promotes corneal allograft rejection.
abstract: OBJECTIVE
  To identify the role of chemokine receptor 6 (D6) expression by dendritic cells (DCs) and its role in corneal transplant immunity.
  
  
  METHODS
  Flow cytometry analysis was used to assess the expression level of the D6 chemokine receptor in different leukocyte populations and DC maturation following lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from wild-type (WT) or D6(-/-) mice (C57BL/6 background). Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed with bone marrow-derived DCs from WT or D6(-/-) mice to evaluate T-cell alloreactivity. Adoptive transfer experiments with T cells from WT or D6(-/-) hosts with BALB/c corneal allografts were performed. Graft opacity was assessed over an 8-week period, and graft survival was plotted using Kaplan-Meier survival curves.
  
  
  RESULTS
  Expression of the D6 chemokine receptor was significantly higher in DCs compared to other leukocyte subpopulations, including neutrophils, lymphocytes, and monocytes/macrophages. LPS challenge of D6(-/-) bone marrow-derived DCs elicited significantly lower levels of major histocompatibility complex II and costimulatory molecules (CD40, CD80, and CD86) compared to WT bone marrow-derived DCs, indicating the role of the D6 chemokine receptor in DC maturation. Further, DCs isolated from D6(-/-) mice induced less T-cell proliferation (p≤0.001) and interferon-gamma production in T cells of draining lymph nodes compared to WT mice following corneal transplantation (p≤0.001). Moreover, adoptively transferred T cells from D6(-/-) corneal transplanted mice to WT mice led to impaired graft rejection, compared to the hosts that received T cells from the WT transplanted mice.
  
  
  CONCLUSIONS
  We demonstrated D6 chemokine receptor expression by DCs and identified its critical function in multiple aspects of DC biology, including maturation and consequent elicitation of alloreactive T-cell responses that are responsible for corneal allograft rejection.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Hajrasouliha
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sadrai
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hyung K
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016039:Corneal Transplantation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression / Q000276:immunology*; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous; D000097628:Chemokine Receptor D6
chemical_list: D015703:Antigens, CD; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6