Pulmonary-intestinal cross-talk in mucosal inflammatory disease

Abstract

Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively. They share many similarities in epidemiological and clinical characteristics, as well as in inflammatory pathologies. Importantly, both conditions are accompanied by systemic comorbidities that are largely overlooked in both basic and clinical research. Therefore, consideration of these complications may maximize the efficacy of prevention and treatment approaches. Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD. We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues.

Figure 1

Possible mechanisms of respiratory-gastrointestinal cross-talk include: overproduction of proteases during excessive inflammation, changes in immune cell function, including increases in cytochrome oxidase (CytOx) expressing lymphocytes and gut originating T cell mis-homing. Cigarette smoke exposure may play a role in organ cross-talk by affecting these processes, and/or by causing mis-homing of dendritic cells (DC) and epithelial cell apoptosis in respiratory or gastrointestinal tissues. Smoke exposure may also lead to changes in the microbiome, promoting growth of enteric bacteria in the lung or altering the microbiome in the intestine that induces inflammatory responses. Inflammation may lead to the production of autoimmune antibodies against the ubiquitous mucosal protein elastin or autoimmune responses against antigens produced during smoke-induced oxidative DNA damage. Systemic IL-6, in conjunction with localized TGF-β, may drive cross-organ Th17 polarized inflammation. Systemic IL-13 may drive aberrant NKT and macrophage responses across organs.