Th17 profile in COPD exacerbations

Abstract

COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow. It is mainly associated with exposure to cigarette smoke. In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide. Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells. Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways. The aims of these molecules are differentiation, proliferation and recruitment of neutrophils. Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight. In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract. Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.

Friend or Foe: The Protective and Pathological Roles of Inducible Bronchus-Associated Lymphoid Tissue in Pulmonary Diseases

“…In most cases, regardless of the Ag or triggering signals, a sustained inflammatory response with an influx of granulocytes, such as neutrophils, eosinophils, and basophils as well as inappropriately activated T and B cells, yields detrimental consequences for the host (6,(56)(57)(58). During chronic inflammatory conditions, IL-17 and LTa likely play a similar early role in driving iBALT induction as during protective iBALT formation.…”

“…COPD is associated with a mixture of Th1, Th2, and Th17 responses, which contribute to worsened disease condition and are exacerbated in the presence of iBALT in both human and mice models (56,58,(69)(70)(71). Particularly, IL-18, a proinflammatory cytokine derived mainly from epithelial cells and myeloid cells, was shown to be associated with worsened lung pathology during COPD by a mechanism involving induction of high levels of IFN-g-producing Th1 cells, which contributed to exacerbated inflammation and disease severity (72).…”

“…Particularly, IL-18, a proinflammatory cytokine derived mainly from epithelial cells and myeloid cells, was shown to be associated with worsened lung pathology during COPD by a mechanism involving induction of high levels of IFN-g-producing Th1 cells, which contributed to exacerbated inflammation and disease severity (72). IL-17-producing Th17 cells, along with IL-1b, are thought to be the main drivers of neutrophilic inflammation in COPD (58,71,73) by a mechanism involving upregulation of the B cell-and T cell-attracting chemokine CXCL12. Furthermore, high serum levels of IL-17 correlated with exacerbated disease and increased numbers of circulating neutrophils in COPD patients (73).…”

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning

“…Th17 cells participate in immunity against extracellular bacteria and recruit neutrophils to the inflammation zone. Therefore, in COPD patients, these cells could be an important factor of the onset of exacerbations, which are defined as worsening of the daily symptomatology that requires modifications in the treatment 1,20 . Therefore, due to the significant mortality and the impact on the quality of life caused by exacerbations in this kind of patient, it is necessary to investigate genetic susceptibility to COPD and COPD exacerbations.…”

Biologics for Chronic Obstructive Pulmonary Disease: Present and Future

“…Elements of the innate immune system include mucociliary clearance, tight junctions, circulating receptor molecules, and phagocytic cells 12,14 . A key physical change induced by the toxic particles in cigarette smoke is impaired elimination of pathogens caused by the shortening of cilia, which reduces the mobility of mucus produced by goblet cells 15 . Smoking also causes hyperplasia of mucus-producing goblet cells, and metaplasia of basal cells and squamous epithelial cells 14,15 .…”