CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways

Resident memory T cells (T_RM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung T_RM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial T_RM cells have distinct effector functions and that CXCR6 controls the partitioning of T_RM cells within the lung by recruiting CD8 T_RM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 T_RM cells due to altered trafficking of CXCR6^-/- cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 T_RM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway T_RM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of T_RM cells to different compartments of the lung and maintains airway T_RM cells.