CCL21 is sufficient to mediate DC migration, maturation and function in the absence of CCL19.
Mice deficient in CCR7 signals show severe defects in lymphoid tissue architecture and immune response. These defects are due to impaired attraction of CCR7+ DC and CCR7+ T cells into the T zones of secondary lymphoid organs and altered DC maturation. It is currently unclear which CCR7 ligand mediates these processes in vivo as CCL19 and CCL21 show an overlapping expression pattern and blocking experiments have given contradictory results. In this study, we addressed this question using CCL19-deficient mice expressing various levels of CCL21. Complete deficiency of CCL19 and CCL21 but not CCL19 alone was found to be associated with abnormal frequencies and localization of DC in naïve LN. Similarly, CCL19 was not required for DC migration from the skin, full DC maturation and efficient T-cell priming. Our findings suggest that CCL21 is the critical CCR7 ligand regulating DC homeostasis and function in vivo with CCL19 being redundant for these processes.
Britschgi
Mirjam R
MR
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Favre
Stéphanie
S
Luther
Sanjiv A
SA
D000483:Alleles; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D054415:Chemokine CCL19 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054421:Chemokine CCL21 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000637:transplantation; D018628:Gene Dosage; D005786:Gene Expression Regulation; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D054400:Receptors, CCR7 / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology
C515461:Ccl19 protein, mouse; C515480:Ccl21a protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7