Effects of Aryl Hydrocarbon Receptor Activation on Pulmonary Innate Lymphoid Cells and Dendritic Cells.

Innate lymphoid cells (ILCs) are a unique group of innate immune cells present in small numbers in mucosal tissues. Increasing evidence suggests that ILC3s not only contribute to chronic inflammation, but may also mediate tissue repair in the lung.  However, those mechanisms responsible for ILC regulation remain to be determined. Because differential production of pro- vs. anti-inflammatory cytokines (e.g. IL-17 vs. IL-22) is strongly dependent on signaling though the AhR, we hypothesize that activation of AhR signaling is a key mechanism regulating the function of pulmonary ILC3s. In this study, we investigated the effects of AhR activation on the phenotype and function of ILCs from C57Bl/6 and AhR^d mice. AhR activation results in the expansion and activation of ILCs, as measured by increased presence of ILCs in the interstitium of the lung, augmented fluorescent intensity of cell surface activation markers, and enhanced production of cytokines, as demonstrated in IL-22^tomato reporter mice. This activation was dependent on AhR expression, and more importantly dependent on AhR expression in CD11c⁺dendritic cells (DCs).  These novel data suggest that DCs may be potent regulators of ILC activation in the lung and that targeting DCs with select AhR ligands may be a viable therapeutic approach to inflammatory lung diseases such as asthma.

This work is supported by NIEHS/NIGMS grant R01-ES013784 (DMS) and NIEHS grant R15-ES020993 (CAB), as well as NIGMS grants P30GM103338 and P20GM103546. This publication is solely the responsibility of the authors and does not necessarily represent the views of NIEHS, NIGMS or NIH.