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

Author(s)

Fernandes, Paula ^[1] ; Oliveira, Luana de Mendonca ^[2] ; Bruggemann, Thayse Regina ^{[3, 4]} ; Sato, Maria Notomi ^[2] ; Olivo, Clarice Rosa ^{[1, 5]} ; Arantes-Costa, Fernanda Magalhaes ^{[1, 6]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Dept Med, Lab Expt Therapeut LIM20, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Clin Dermatol, Lab Med Invest LIM56, Sao Paulo - Brazil

^[3] Harvard Med Sch, Boston, MA 02115 - USA

^[4] Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Med Div, 75 Francis St, Boston, MA 02115 - USA

^[5] Univ City Sao Paulo UNICID, Inst Med Assistance State Publ Servant IAMSPE, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, CEDEM, Dept Med, Ctr Dev Med Educ, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 10, MAY 16 2019.
• Web of Science Citations: 0

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-beta 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-beta. 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. (AU)

• FAPESP's process: 14/21395-6 - The role of dendritic cells in the immunomodulation induced by cigarette smoke in a murine model of chronic allergic lung inflammation
• Grantee: Fernanda Magalhães Arantes Costa
• Support Opportunities: Regular Research Grants