iNKT cell-mediated XCL1-XCR1 axis promotes allergic airway hyperresponsiveness by recruiting CD103+ dendritic cells

Publication date: Available online 21 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Yeon Duk Woo, Jaemoon Koh, Hye-Ryun Kang, Hye Young Kim, Doo Hyun Chung
BackgroundThe XCL1–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 allergic asthma.ObjectiveIn the present study, we explored that the iNKT cell-mediated XCL1–XCR1 axis regulated the allergic asthma.MethodsOvalbumin (OVA) or house dust mite (HDM)-induced asthma was developed in XCL1 or XCR1 knockout (KO) mice.ResultsXCL1 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 HDM-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 in vitro and in vivo. Upon 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 Th2 responses in the lungs of CD1d KO mice during OVA-induced asthma, whereas that of XCL1-deficient iNKT cells did not. In human, the percentages and XCL1 production capacity of iNKT cells from peripheral blood mononuclear cells were higher in patients with asthma than healthy control.ConclusionThese data demonstrate that the iNKT cell-mediated XCL1–XCR1 axis promotes AHR by recruiting CD103⁺ DCs into the lung in allergic asthma.

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