title: Blocking CCR7 at the ocular surface impairs the pathogenic contribution of dendritic cells in allergic conjunctivitis.
abstract: CCR7 plays a key role in mobilizing tissue dendritic cells (DCs) to the lymphoid compartment for consequent elicitation of adaptive immunity. Interfering with CCR7 function therapeutically would therefore be anticipated to inhibit the progression of atopic conditions, for example, allergic conjunctivitis (AC). However, the CCR7-CCL19/CCL21 system in the ocular surface is poorly understood as is the precise role of DCs in AC immunopathogenesis. T cells from ovalbumin (OVA)-primed mice were adoptively transferred into wild-type (WT) hosts. Exogenous WT (eGFP(+)) versus CCR7(-/-) DCs were engrafted subconjunctivally (SCJ), and hosts were challenged with OVA (Texas-Red+) eye drops. AC immunopathogenesis was evaluated via clinical examinations, infiltration of mast cells and eosinophils, Th2 reactivity, and serum IgE levels. AC was also assessed in actively immunized mice challenged with OVA eye drops containing 1% anti-CCR7 antibody or isotype control. In eye-draining lymph nodes (LNs), OVA(+) SCJ engrafted WT DCs conferred upregulated CCR7 and caused augmentation of clinical signs. This result was corroborated by increased conjunctival infiltration, Th2 cytokines in LNs, and serum OVA-specific IgE. Strikingly, this was completely reversed with SCJ engrafted CCR7(-/-) DCs in all parameters tested. Furthermore, topical antibody blockade of CCR7 in actively immunized mice significantly inhibited AC. Ocular surface DCs via CCR7 expression contribute to the immunopathogenesis of AC, thereby allowing significant inhibition of this experimental condition via topical CCR7 antibody blockade.
authors.affiliation: Schepens Eye Research Institute, Boston, MA, USA.
authors.forename: Simona
authors.initials: S
authors.lastname: Schlereth
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Payal
authors.initials: P
authors.lastname: Khandelwal
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003228:Conjunctiva / Q000276:immunology; D003233:Conjunctivitis, Allergic / Q000276:immunology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D007073:Immunoglobulin E / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009883:Ophthalmic Solutions; D010047:Ovalbumin / Q000276:immunology; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; C515371:Ccr7 protein, mouse; D009883:Ophthalmic Solutions; D054400:Receptors, CCR7; D007073:Immunoglobulin E; D010047:Ovalbumin