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 T_H2 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 α-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_H2 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.