Aerobic exercise attenuates airway inflammation in allergic asthma by regulating M2 macrophage polarization via drp1-mediated mitophagy

  • Immunol Lett. 2026 Oct:281:107198. doi: 10.1016/j.imlet.2026.107198.
Linfang Ding  1 Nannan Wu  2 Jie Lin  3
Affiliations
  • 1. Outpatient nursing, The Second Hospital of Jiaxing City, Jiaxing 314000, China.
  • 2. Department of Laboratory Medicine, Tianjin Chest Hospital, Tianjin 300222, China.
  • 3. Outpatient nursing, The Second Hospital of Jiaxing City, Jiaxing 314000, China. Electronic address: [email protected].
Abstract

Allergic asthma is a chronic respiratory condition characterized by persistent airway inflammation and dysregulated macrophage activation. Although aerobic exercise is known to exert anti-inflammatory effects, its influence on macrophage polarization and mitochondrial dynamics in asthma remains poorly defined METHODS: Using a rat model of ovalbumen (OVA)-induced allergic asthma, we investigated the impact of aerobic exercise on macrophage polarization and Mitophagy regulation. Animals were divided into four experimental groups: control, OVA-induced asthma, OVA with aerobic exercise intervention, and OVA with Drp1 inhibitor (Mdivi-1) treatment. We evaluated airway inflammation, macrophage phenotypes, mitochondrial function, and key mitophagy-related proteins RESULTS: Aerobic exercise significantly attenuated allergic airway inflammation, as evidenced by reduced inflammatory cell infiltration, decreased mucus production, and a shift in macrophage polarization from the M2 towards the M1 phenotype. At the molecular level, exercise suppressed Mitophagy activation, reduced Drp1 phosphorylation, and downregulated the expression of mitophagy-related proteins. These effects were mirrored by Drp1 inhibition with Mdivi-1, confirming the crucial role of Drp1-mediated Mitophagy in exercise-induced modulation of macrophage polarization CONCLUSION: Our findings indicate that aerobic exercise alleviates allergic airway inflammation by inhibiting Drp1-dependent Mitophagy and rebalancing macrophage polarization. These results provide novel mechanistic insights into the therapeutic potential of exercise in asthma and highlight Mitophagy as a promising target for inflammatory respiratory diseases.

Keywords
Aerobic exercise; Airway inflammation; Allergic asthma; Drp1; Macrophage polarization; Mitophagy.
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