Physical Exercise Induces Immunoregulation of TREG, M2, and pDCs in a Lung Allergic Inflammation Model

Abstract

The benefits of moderate aerobic physical exercise for allergic asthma are well-known, particularly that of the anti-inflammatory effect that occurs by reducing Th2 responses and lung remodeling. However, the mechanisms of this immunoregulation are still under investigation. In this study, we investigated the possible immunoregulatory mechanisms of lung inflammation induced by moderate aerobic exercise in an experimental asthma model. BALB/c mice were distributed into Control, Exercise (EX), OVA, and OEX groups. OVA and OEX groups were sensitized with ovalbumin (OVA) on days 0, 14, 21, 28, and 42 and were challenged with OVA aerosol three times a week from days 21 to 51. The EX and OEX groups underwent moderate aerobic physical exercise from days 21 to 51 (5 d/w, 1 h/d). The mice were euthanized on day 52. We evaluated pulmonary cytokine production, serum immunoglobulin levels, and the inflammatory cell profile in lung and mediastinal lymph nodes. OVA mice showed increased expression of IL-4, IL-6, IL-10, and TGF-β and decreased macrophage type 2 (M2) recruitment. Physical exercise did not affect the increased antibody production of IgG2a, IgG1, or IgE induced by OVA. Of note, physical exercise alone markedly increased production of anti-inflammatory cytokines such as IL-10 and TGF-β. Physical exercise in OVA-mice also increased the recruitment of M2 in the lungs, as well as the influx and activation of regulatory T cells (Tregs) and CD4 and CD8 lymphocytes. In the draining lymph nodes, it was also observed that physical exercise increased the activation of CD4 T cells, regardless of the presence of OVA. Notably, physical exercise decreased common dendritic cells' (cDCs; pro-inflammatory) expression of co-stimulatory molecules such as CD80, CD86, and ICOSL in the draining lymph nodes, as well as increased ICOSL in plasmacytoid dendritic cells (pDCs; anti-inflammatory). Together, these findings show that physical exercise modulates pulmonary allergic inflammation by increasing Treg and M2 recruitment, as well as pDCs activation, which leads to an increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cells and mediators.

High-intensity resistance training in newly diagnosed sarcoidosis- an exploratory study of effects on lung function, muscle strength, fatigue, dyspnea, health-related quality of life and lung immune cells

“…In sarcoidosis, the exaggerated inflammatory response has, at least partly, been explained by a dampened function and/ or reduced frequency in BALF and blood of T regs . Interestingly, in a mice model of asthma, physical exercise caused an increase of activated T regs in the lungs [37]. Thus, a possible explanation for the positive effect of training could be restoration of a dysregulated T reg pool.…”

Molecular mechanisms involved in the positive effects of physical activity on coping with COVID-19

“…The anti-inflammatory response induced by regular PA is mediated by skeletal muscle contraction through the release of muscle-derived cytokines (myokines). Moderate PA induces a marked increase in serum levels of cytokines involved in the regulation of inflammation, such as IL-10, IL-1 receptor antagonist (IL-1ra), and IL-37 (Pedersen and Febbraio 2008 ; Fernandes et al 2019 ; Abbasi et al 2014 ; Nold et al 2010 ). On the other hand, another myokine, IL-6, acts in suppressing the secretion of pro-inflammatory cytokines in several tissues, contributing to the creation of an anti-inflammatory environment for several hours after exercise.…”

Defining a role for exercise training in the management of asthma

“…The mechanisms of how exercise exerts its anti-inflammatory effects in this simplified mouse model of asthma remain unclear, although reduced NF-κB activation [23], increases in glucocorticoid receptor expression [24], FoxP3 increases [27], T-cell trafficking in response to an allergen challenge [30] with increased lung recruitment of Tregs and macrophages [33], and increased IL-10 and IL-1ra have been proposed [25,21], with IL-10 increases recently directly linked with increases in M2 macrophages in the lung tissue [33].…”

“…Alterations in airway epithelium are important in inflammation and airway remodelling in asthma. VIEIRA et al [33] investigated the effects of aerobic exercise on airway epithelial cells in OVA-sensitised mice and showed that low-intensity aerobic exercise reduced oxidative and nitrosative stress. There was reduced epithelial expression of NF-κB and P2X7R (a plasma membrane receptor involved in control of proinflammatory cytokine expression) and increased expression of epithelial IL-10.…”