COPD immunopathology

Abstract

The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking. In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations. This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways. This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.

IL‐33 induces production of autoantibody against autologous respiratory epithelial cells: a potential mechanism for the pathogenesis of COPD

“…Finally, as referred to in recent overviews of the possible role of autoimmune immunological reactions in the pathogenesis of COPD, there remains the issue of causality . Our present data are consistent with the hypothesis that airways tissue damage in a local IL‐33‐rich environment results in the production of autoantibodies that sustain this damage and are potentially responsible for the development of at least some of the pathological features of COPD, such as progressive alveolar destruction.…”

“…The fact that the percentages of Tfh cells and B2 B‐cells were positively correlated in the mediastinal lymph nodes further suggests the possibility that the B2 B‐cells producing the antibodies are propagated locally at this site. Further, challenge of the animals with IL‐33 along with lysate, but neither alone, resulted in local, elevated expression of IL‐6, which has been implicated in inducing differentiation of primary T‐cells to Tfh cells . Recent findings suggest that IL‐33 may also induce the development of Tfh cells …”

“…It is a potentially devastating lung disease characterized by progressive, irreversible airways obstruction reflecting inflammation and remodelling and, in some patients, impaired gas transfer secondary to pulmonary alveolar destruction. [1][2][3][4][5] Inhalation of environmental smoke, typically from cigarette smoking or open fires, has been recognized for some decades as a key risk factor for the development of COPD, although only approximately 25% of smokers by the age of 80 years develop the disease, 6 while only approximately half of all patients diagnosed with COPD have a clear history of smoking or smoke exposure, suggesting alternative environmental triggers of the disease. Another phenomenon that remains largely unexplained is the fact that pulmonary inflammation and impairment of lung function may persist and progress even after cessation of smoke exposure, 8 suggesting environmental initiation of a more persistent process independent of the original trigger.…”

Targeting Transcription Factor Lysine Acetylation in Inflammatory Airway Diseases

“…For asthma, the clinical symptoms include among others wheezing and shortness of breath. COPD is characterized by shortness of breath upon exercise and a largely irreversible and progressive airflow limitation [1][2][3][4]. In asthma the larger airways are mainly affected, whereas in COPD, the lung parenchyma and peripheral airways are mainly affected [3].…”

“…Severe asthmatics display glucocorticoid resistance [6], and the effectivity of glucocorticoids in COPD patients is subject to debate [7,8]. Alternative therapeutic strategies are needed for these patients, which currently form a major health burden for society due to high socioeconomic costs [1][2][3][4]9]. Studying the underlying molecular mechanisms may enable the identification of new therapeutic targets.…”