Regulation in chronic obstructive pulmonary disease: the role of regulatory T-cells and Th17 cells

Abstract

COPD (chronic obstructive pulmonary disease) is an inflammatory disorder of the airways, which is associated with irreversible airway obstruction. The pathological hallmarks of COPD are destruction of the lung parenchyma (pulmonary emphysema), inflammation of the central airways (chronic bronchitis) and inflammation of the peripheral airways (respiratory bronchiolitis). Tobacco smoking is established as the main aetiological factor for COPD. A maladaptive modulation of inflammatory responses to inhalation of noxious particles and gases is generally accepted as being a key central pathogenic process; however, the precise regulatory mechanisms of the disease are poorly understood. Two cell types are known to be important in immune regulation, namely regulatory T-cells and the newly identified Th17 (T-helper 17) cells. Both types of cells are subsets of CD4 T-lymphocytes and modulate the immune response through secretion of cytokines, for example IL (interleukin)-10 and IL-17 respectively. The present review will begin by describing the current understanding of inflammatory cell involvement in the disease process, and then focus on the possible role of subsets of regulatory and helper T-cells in COPD.

Interleukin-17A is involved in development of spontaneous pulmonary emphysema caused by Toll-like receptor 4 mutation

“…However, there have also been some reports that are opposed to the above-mentioned results regarding the association between IL-17A and emphysema. Others have indicated that airway infiltration of CD4 + CCR6 + Th17 cells are associated with chronic cigarette smoke induced airspace enlargement [30,31] . Four-month exposure to smoke, a major stimulator of emphysema, can induce significant increases in IL-17 levels in the pulmonary airway [32] .…”

Reasonability and perspectives of anti-cytokine and immune correcting therapy in patients with chronic obstructive pulmonary disease

“…К Th17 клеткам относятся CD4 + T лимфоциты, для которых характерна секреция IL 17A, IL 17F и IL 22 [71,72]. Кроме того, IL 17 синтезируется естествен ными киллерами, цитотоксическими Т лимфоцита ми и гранулоцитами.…”

“…Кроме того, IL 17 синтезируется естествен ными киллерами, цитотоксическими Т лимфоцита ми и гранулоцитами. IL 17 опосредованно способ ствует привлечению нейтрофилов и лимфоцитов из крови в очаг воспаления в легких путем стимуляции секреции провоспалительных хемокинов IL 8, CCL20 и CXCL10 эпителиальными клетками возду хоносных путей и альвеолярными макрофагами [71,73,74]. Кроме того, этот цитокин стимулирует обра зование MMP 9 в клетках эпителия дыхательных пу тей [75].…”

“…Другой подход к блокированию синтеза IL 17 связывают с ингибированием IL 23, поскольку этот цитокин способствует развитию и активации попу ляции Th17 клеток [71,72,79]. Для лечения пациен тов со средней и тяжелой степенью бляшечного псо риаза в РФ и Беларуси официально зарегистрирован препарат устекинумаб, представляющий собой мо ноклональные антитела к общей субъединице p40 в составе IL 23.…”

Evasion of COPD in smokers: at what price?

“…A deficiency of Tregs can impair the immune system tolerance for autoantigens and lead to autoimmune disease [15]. The behaviour of Tregs in COPD is of interest and seems to vary with the site in the lung and severity of the population studied [16]. Long-term smoking exposure, but not the development of airflow obstruction, increases Treg numbers in the lung [17].…”