Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease.
BACKGROUND
Chemokine receptors (CR) play an important role in T cell migration, but their contribution to lung trafficking is unclear.


OBJECTIVE
We hypothesized that if a particular CR was involved in T cell homing its expression would be enriched on lung T cells compared with peripheral blood T cells (PBT).


METHODS
We have measured the CR expression on BAL T cells from patients with sarcoid, other interstitial lung diseases (ILD), asthma and healthy volunteers.


RESULTS
Of 14 CR studied in sarcoid, CXCR6 expression was the most markedly increased in the lung compared with the blood, a finding that was also seen in ILD patients. A striking although lesser increase was also seen in asthmatics and healthy controls. Analysis of expression of the CXCR6 ligand, CXCL16, by immunohistochemistry suggested that alveolar macrophages (AM) were the major source of CXCL16 in the lung. AM expressed mRNA for CXCL16 and released nanogram quantities after adhesion to plastic as shown by RT-PCR, Western blotting and ELISA. Bronchoalveolar lavage (BAL) fluid from all subjects contained large amounts of CXCL16. The full-length CXCL16 was the predominant isoform in AM lysates, supernatants and BAL.


CONCLUSIONS
This data suggests that CXCR6 and CXCL16 may play a role in T cell recruitment to the lung.
Morgan
A J
AJ
Institute for Lung Health, Department of Infection, Immunity and Inflammation, Leicester University, Glenfield Hospital, Leicester, UK.
Guillen
C
C
Symon
F A
FA
Huynh
T T
TT
Berry
M A
MA
Entwisle
J J
JJ
Briskin
M
M
Pavord
I D
ID
Wardlaw
A J
AJ
D000328:Adult; D001249:Asthma / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000032:analysis* / Q000097:blood / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology*; D018655:Lymphocyte Count; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D011658:Pulmonary Fibrosis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis* / Q000097:blood / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000097:blood / Q000235:genetics; D051116:Receptors, Scavenger / Q000032:analysis* / Q000097:blood / Q000235:genetics; D011991:Receptors, Virus / Q000032:analysis* / Q000097:blood / Q000235:genetics; D012507:Sarcoidosis / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry*
D015415:Biomarkers; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D012333:RNA, Messenger; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D051116:Receptors, Scavenger; D011991:Receptors, Virus