Expression of CXCR6 and its ligand CXCL16 in the lung in health and disease

Chemokine receptors (CR) play an important role in T cell migration, but their contribution to lung trafficking is unclear. 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). We have measured the CR expression on BAL T cells from patients with sarcoid, other interstitial lung diseases (ILD), asthma and healthy volunteers. 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. This data suggests that CXCR6 and CXCL16 may play a role in T cell recruitment to the lung.