The invariant natural killer T cell-mediated chemokine X-C motif chemokine ligand 1-X-C motif chemokine receptor 1 axis promotes allergic airway hyperresponsiveness by recruiting CD103(+) dendritic cells

Background: The chemokine X-C motif chemokine ligand 1 (XCL1)-X-C motif chemokine receptor 1 (XCR1) axis has been reported to play a role in immune homeostasis and inflammation. However, it is not known whether this axis has a critical function in patients with allergic asthma. Objective: In the present study we explored whether the invariant natural killer T (iNKT) cell-mediated XCL1-XCR1 axis regulated allergic asthma. Methods: Ovalbumin (OVA)- or house dust mite-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice. Results: XCL1 or XCR1 KO mice showed attenuation in airway hyperresponsiveness (AHR), numbers of CD103(+) dendritic cells (DCs), and TH2 responses in the lungs compared with wild-type (WT) mice during OVA-or house dust mite-induced asthma. These effects were reversed by intratracheal administration of recombinant XCL1 or adoptive transfer of CD103(+) DCs but not CD11b(+) DCs into XCL1 KO mice. Moreover, iNKT cells highly expressed XCL1 both in vitro and in vivo. On intranasal alpha-galactosyl ceramide challenge, CD103(+) DC numbers in the lungs were increased in WT but not XCL1 KO mice. Furthermore, adoptive transfer of WT iNKT cells increased AHR, CD103(+) DC recruitment, and T(H)2 responses in the lungs of CD1d KO mice during OVA-induced asthma, whereas adoptive transfer of XCL1-deficient iNKT cells did not. In human patients, percentages and XCL1 production capacity of iNKT cells from PBMCs were greater in patients with asthma than in healthy control subjects. Conclusion: These data demonstrate that the iNKT cell-mediated XCL1-XCR1 axis promotes AHR by recruiting CD103(+) DCs into the lung in patients with allergic asthma.