title: A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.
abstract: Lymphocyte recruitment to peripheral tissues is fundamental for immune surveillance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. To address this, we analyzed the chemokines expressed in the normal human nasal mucosa and found that CCL28 is preferentially expressed at a high level on the lumenal face of vascular endothelial cells in the mucosa. Analysis of the cognate chemokine receptors revealed that close to 50% of the CD4(+) T cells in the human nasal mucosa expressed the CCL28 receptor CCR3, whereas CCR3 was hardly detectable on T cells in the small intestine and skin. In the circulation, CCR3(+) T cells comprised a small subset that did not express homing receptors to the intestine or skin. Moreover, depletion of CCR3(+)CD4(+) T cells abrogated the proliferative response of human blood CD4(+) T cells against the opportunistic nasopharyngeal pathogen Haemophilus influenzae, indicating that the CCR3(+)CD4(+) T-cell subset in the circulation contains antigen specificities relevant for the upper airways. Together, these findings indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.
authors.affiliation: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Danilova
authors.affiliation: 1] Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway [2] Department of Otorhinolaryngology, Akershus University Hospital, Nordbyhagen, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Skrindo
authors.affiliation: Department of Otolaryngology, Lovisenberg Diakonale Hospital, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Gran
authors.affiliation: Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hales
authors.affiliation: Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia.
authors.forename: W A
authors.initials: WA
authors.lastname: Smith
authors.affiliation: Department of Gastroenterology, Akershus University Hospital, Nordbyhagen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Jahnsen
authors.affiliation: 1] Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway [2] Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: F E
authors.initials: FE
authors.lastname: Johansen
authors.affiliation: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: F L
authors.initials: FL
authors.lastname: Jahnsen
authors.affiliation: Department of Pathology and Centre for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
authors.forename: E S
authors.initials: ES
authors.lastname: Baekkevold
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D054397:Receptors, CCR3 / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; C414047:CCL28 protein, human; C515350:CCR3 protein, human; D019742:Chemokines, CC; D054397:Receptors, CCR3; D016201:Receptors, Lymphocyte Homing