CD1d-Restricted IFN-γ-Secreting NKT Cells Promote Immune Complex-Induced Acute Lung Injury by Regulating Macrophage-Inflammatory Protein-1α Production and Activation of Macrophages and Dendritic Cells

Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and J alpha 18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by alpha-galactosyl ceramide. IFN-gamma and MIP-1 alpha production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-gamma-, MIP-1 alpha-, or Fc gamma R-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-gamma R deficient NKT cells enhanced MIP-1 alpha production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-) IFN-gamma mice, but to a lesser extent than WT NKT cells. This suggests that IFN-gamma producing NKT cells enhance MIP-1 alpha production in both an autocrine and a paracrine manner. IFN-gamma deficient NKT cells induced less IL-1 beta and TNF-alpha production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-gamma producing NKT cells promote IC-ALI by producing MIP-1 alpha and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells. The Journal of Immunology, 2011, 186: 1432-1441.