title: CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells.
abstract: The follicle-associated epithelium (FAE) secretes chemokines important in the recruitment of various cell types including CCL20 (MIP-3alpha). CCL20 is chemotactic to the CD11b(+) dendritic cells (DCs) distributed in the subepithelial dome regions of the Peyer's patches, and mice deficient in the receptor for CCL20, CCR6, have been reported to be devoid of the CD11b(+) DCs in the dome regions. Here, we describe another chemokine specifically secreted from the FAE of mouse Peyer's patches, CCL9 (MIP-1gamma, CCF18, MRP-2). By in situ hybridization, we demonstrated that CCL9 mRNA was expressed by the FAE but not by the villus epithelium. At the protein level, CCL9 was detected on the FAE and on extracellular matrix structures within the dome regions of the Peyer's patches. By RT-PCR, we demonstrated that one of the putative receptors for CCL9, CCR1, was expressed by the Peyer's patch CD11b(+) DCs and in a chemotaxis assay, CD11b(+) DCs migrated toward CCL9. To compare the abilities of the chemokines CCL20 and CCL9 to recruit CD11b(+) DCs to the dome regions, we examined the in vivo distribution of these cells in CCR6-deficient, CCL9-blocked wild type, or CCL9-blocked CCR6-deficient mice. To our surprise, using a sensitive immunofluorescence analysis, we observed that CD11b(+) DCs were present in the dome regions of the CCR6-deficient mice. In contrast, Ab neutralization of CCL9 in vivo resulted in significant reduction of the CD11b(+) DC number in the subepithelial dome regions of Peyer's patches of both wild type and CCR6 -/- mice. Taken together, these results demonstrate an important role of CCL9 in CD11b(+) DC recruitment to the dome regions of mouse Peyer's patches.
authors.affiliation: Department of Epidemiology and Public Health and Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Zhao
authors.forename: Ayuko
authors.initials: A
authors.lastname: Sato
authors.forename: Charles S
authors.initials: CS
authors.lastname: Dela Cruz
authors.forename: Melissa
authors.initials: M
authors.lastname: Linehan
authors.forename: Andreas
authors.initials: A
authors.lastname: Luegering
authors.forename: Torsten
authors.initials: T
authors.lastname: Kucharzik
authors.forename: Aiko-Konno
authors.initials: AK
authors.lastname: Shirakawa
authors.forename: Gabriel
authors.initials: G
authors.lastname: Marquez
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
authors.forename: Ifor
authors.initials: I
authors.lastname: Williams
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000494:pharmacology; D039481:CD11b Antigen / Q000096:biosynthesis*; D002464:Cell Migration Inhibition; D018925:Chemokines / Q000096:biosynthesis; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008871:Microvilli / Q000276:immunology / Q000378:metabolism; D010581:Peyer's Patches / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; D039481:CD11b Antigen; C095218:Ccl9 protein, mouse; D018925:Chemokines; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; C070959:Ccl6 protein, mouse