Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation.
Memory/effector T cells recirculate through extralymphoid tissues by entering from blood and egressing via afferent lymph. Although T cell entry into effector sites is key to inflammation, the relevance of T cell egress to this process is unknown. In this study, we found that Ag recognition at the effector site reduced the tissue egress of proinflammatory Th1 cells in a mouse model of delayed hypersensitivity. Transgenic expression of "tissue exit receptor" CCR7 enhanced lymphatic egress of Ag-sequestered Th1 cells from the inflamed site and alleviated inflammation. In contrast, lack of CCR7 on Th1 cells diminished their tissue egress while enhancing inflammation. Lymph-borne Th1 and Th17 cells draining the inflamed skin of sheep migrated toward the CCR7 ligand CCL21, suggesting the CCR7-CCL21 axis as a physiological target in regulating inflammation. In conclusion, exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress as a novel control point of inflammation.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Daniela
D
Gómez
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Malissa C
MC
Diehl
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Erika J
EJ
Crosby
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Tiffany
T
Weinkopff
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 gdebes@vet.upenn.edu.
Gudrun F
http://orcid.org/0000-0003-4208-7362
GF
Debes
D000818:Animals; D000941:Antigens / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054421:Chemokine CCL21 / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D000941:Antigens; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D054400:Receptors, CCR7