Lung disease causes premature aging of the immune system, study suggests

Research developed at the Faculty of Medicine of the University of São Paulo (FM-USP) and published in the journal Immunity & Aging places chronic obstructive pulmonary disease (COPD) among those that lead to premature aging of the immune system. The finding may be a way to explain why individuals with the disease have a lower response to vaccines and are more susceptible to infectious processes, for example.

The researchers concluded that COPD patients have a set of changes linked to cellular aging, a process called immunosenescence, which affects CD4+ and CD8+ T lymphocytes, impairing the immune response.

To carry out the study, 92 people were recruited, divided into four groups: patients with COPD, smokers without evidence of lung disease, healthy elderly and young adults. The scientists analyzed seven markers associated with late differentiation, senescence and cell exhaustion for each of these groups.

They concluded that patients with chronic obstructive pulmonary disease have cells that express a full range of senescent or depleted phenotypes, consistent with features of premature aging of the immune system.

COPD is a chronic inflammatory disease characterized by airflow obstruction and commonly induced by cigarette smoke and air pollution. It affects about 64 million people worldwide, according to an estimate by the World Health Organization (WHO), with approximately 6 million in Brazil, of which 60% of cases would be smokers or ex-smokers.

“With the increase in the elderly population, understanding the mechanisms involved in immunosenescence is important in several aspects. Understanding how to deal with the body of these people, more prone to cancers, infections and less responsive to vaccines, can open paths to seek a better functioning of the immune system. This work helps to understand what happens and where it is possible to try to act”, explains professor Gil Benard, from the Laboratory of Dermatology and Immunodeficiencies at FM-USP and supervisor of the study, which had the support of Fapesp.

First author of the research, the result of her doctorate, Juliana Ruiz Fernandes explains that, when comparing data from people of the same age, those with COPD had accelerated T cell aging. “The lymphocyte phenotype of these individuals seems older compared to those who do not have the chronic inflammatory process”, Fernandes tells Agência Fapesp.

In the group of smokers, the results suggest that moderate to heavy chronic smoking did not accelerate the pace of immunosenescence compared to healthy older adults. “COPD ended up interfering more in patients than age, drastically affecting the immune system”, completes doctoral student Thalyta Nery Carvalho Pinto, also author of the article.

In his master’s thesis, in 2016, Fernandes had shown the effect of physical exercise on the immune response of patients with COPD, concluding that the rehabilitation program was able to slow down some parameters of cellular senescence, improving the immune response of lymphocytes.

At the time, the results already suggested that individuals with the disease had a higher proportion of cells with an exhaustion profile and lower functional capacity. “We are now trying to understand the cell types involved in COPD and in the elderly”, says the researcher.

To understand

Immunosenescence is marked by a decrease in total young T cells (called naive by scientists) and an increase in memory lymphocytes, which have three phase dynamics during human life.

The first is characterized by a pool of young cells, which over time become memory cells in response to stimulation with specific antigens. The second phase (called memory homeostasis) is characterized by the circulation of memory T cells, which reach a plateau and are maintained throughout adulthood.

In the third step, after a long period of stability, the frequency and functionality of memory T cells change, increasing susceptibility to infections caused by immune dysregulation as part of the physiological decline.

In the work, the researchers detected a “disorder” in this cycle of the immune system in patients with COPD. They had not only a reduced pool of naive cells available for immune responses, but also, paradoxically, increased fractions of these cells with characteristics of differentiation, senescence or exhaustion when compared to healthy elderly people and smokers.

“We also saw that immunosenescence and alterations recorded in individuals with COPD are more pronounced in CD8+ T lymphocytes, which act as a kind of ‘soldier’ ​​responsible for executing the immune response in the human body”, says Benard.

Now, with a different sample of individuals from the previous one, the group of scientists is studying how type B lymphocytes respond in COPD patients. It also seeks to assess how these people are responding to the Covid-19 vaccine.