Activation of the Src family kinase, haematopoietic cell kinase (Hck), promotes inflammatory disease and airspace enlargement in the lungs of mice similar COPD in humans1, in addition mutations in Hck have been observed in lung cancer. This study used a genetic complementation approach to investigate the contribution of the adaptive immune system, TNF-α, and MyD88 to inflammation in Hck mutant mice (Hck499F). Inflammation was characterised by bronchoalveolar lavage (BAL) and cytokine measurements derived from recovered BAL fluid. Macrophage proliferation was assessed by macrophage colony forming assay using bone marrow and pulmonary-derived cells isolated from wt and Hck499F mutant mice and macrophage phenotype was assessed by gene expression analysis in cells recovered from BAL. Pulmonary adenoma formation was assessed in Cre inducible KrasG12D mutant mice by image analysis. Hck499F mice developed pulmonary inflammation dominated by macrophages and eosinophils as indicated by an increase BAL fluid cellularity compared to wt mice. A contribution of the adaptive immune system to disease was discounted after lymphocyte and Th2-deficient mice, Hck499F;Rag1-/- and Hck499F;Stat6-/-respectively, showed no reduction in macrophage content of BAL fluid. Genetic depletion of TNF-α or MyD88 rescued the inflammation phenotype of Hck499F mice. Macrophage colony formation assays demonstrated that the Hck499Fmutation increased the differentiation of bone marrow-derived progenitor cells into macrophages and skewed BAL cell gene expression profiles to a tumour associated macrophage (TAM)-like profile. Hck may promote tumour growth as Hck499F;KrasG12D mutant mice had a higher tumour burden than KrasG12D control mice. This study suggests that Hck is involved in macrophage-dominant autoinflammatory pulmonary disease and may promote tumour progression. These phenotypes of Hck499F mice resemble chronic inflammation and cancer development in COPD patients.