Environmental and inflammatory factors influencing concurrent gut and lung inflammation

Background: Crohn’s disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly. Methods: Using the SHIP-1^−/− model of Crohn’s-like ileitis and chronic lung inflammation, the two diseases were co-investigated. Results: Contrary to prior literature, Crohn’s-like ileitis was not fully penetrant in SHIP-1^−/− mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1^−/− mice without overt ileitis was similar to control ilea. However, SHIP-1^−/− mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1^−/− mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1^−/− mice. Conclusions: These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.