title: Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue.
abstract: BACKGROUND
  Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy.
  
  
  OBJECTIVE
  Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration.
  
  
  METHODS
  Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study.
  
  
  RESULTS
  Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26.
  
  
  CONCLUSIONS
  Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway.
authors: Department of Otolaryngology and Head and Neck Surgery, Liege University Hospital-CHU, Liege, Belgium. amrel_shazly@hotmail.com
authors: A E
authors: AE
authors: El-Shazly
authors: H C
authors: HC
authors: Doloriert
authors: B
authors: B
authors: Bisig
authors: P P
authors: PP
authors: Lefebvre
authors: P
authors: P
authors: Delvenne
authors: N
authors: N
authors: Jacobs
mesh_terms: D000485:Allergens; D000073883:CX3C Chemokine Receptor 1; D000075906:Chemokine CCL26; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism; D012852:Sinusitis / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; C120429:CCL26 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D000075906:Chemokine CCL26; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D019707:Receptors, Chemokine; D011505:Protein-Tyrosine Kinases