Fine control of macrophage activation is required to prevent inflammatory disease,particularly at barrier sites such as the lung. However, the dominantmechanisms that regulatepulmonary Ms during inflammation are currently poorly understood. Here we show that airwayMs are substantially less able torespond to the canonical type-2 cytokine IL-4, which underpinsallergic disease and parasite worm infections, than lung tissue or peritoneal cavity Ms.Werevealthat M hypo-responsiveness to IL-4 is dictated by the lung environment, though independent ofthe host microbiota or the prominent lungextracellular matrix components surfactant protein D andmucin 5b. Rather, compared to cavity Ms, airway Ms display severely dysregulatedmetabolism.Strikingly, upon removal from the lung, alveolar Ms regain IL-4 responsiveness in aprocess dependent upon glycolysis. Thus, we propose that impairedglycolysis within thepulmonary niche is a central determinant for regulation of M responsiveness during type-2inflammation. SOURCE: Alasdair Ivens (al.ivens@ed.ac.uk) -  Centre for Immunity, Infection and Evolution

Pluto Bioinformatics

GSE126309: The lung environment controls alveolar macrophage metabolism and responsiveness during type-2inflammation.