Invariant NKT cells recruit CD103+ dendritic cells via XCL1-XCR1 axis, thereby promoting allergic airway resistance

Abstract

Abstract Among immune cells, dendritic cells (DC) and invariant (i) NKT cells are critically implicated in allergic asthma. However, the interaction between two subsets remains elusive in asthma. To address this, we investigated how these two subsets interact and exert regulatory effects on asthma. Upon intranasal inoculation of WT mice with synthetic ligand, a-galactosyl ceramide (a-GalCer), CD103+ DCs were significantly recruited into the lungs in WT but not CD1d KO mice, suggesting that iNKT cells contribute to recruiting CD103+ DCs in the respiratory system. Moreover, microarray assay revealed that iNKT cells highly expressed XCL1, a chemokine for CD103+ DCs expressing XCR1. Consistently, a-GalCer treatment increased production of XCL1 by iNKT cells in vitro and in vivo, and XCL1 KO mice showed a deficiency in iNKT cell-mediated recruitment of CD103+ DCs into the lungs. In the OVA-induced allergic asthma model, XCL1 KO mice attenuated airway resistance, inflammation, CD103+ DC number, and Th2 type immune responses in the lungs. Furthermore, adoptive transfer of XCL1-deficient iNKT cells did not alter airway resistance and recruit CD103+ DCs in CD1d KO mice, whereas WT iNKT cells or CD103+ DCs restored allergic asthma. Taken together, this study demonstrates that iNKT cells crosstalk CD103+ DCs via XCL1-XCR1 axis, thereby promoting allergic asthma.