Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model.
We have reported previously that moderate intensity aerobic exercise training attenuates airway inflammation in a murine asthma model. Recent studies implicate regulatory T (Treg) cells in decreasing asthma-related airway inflammation; as such, the current study examined the effect of exercise on Treg cell function in a murine asthma model. Mice were sensitized with ovalbumin (OVA) prior to the start of exercise training at a moderate intensity 3x/week for 4weeks; exercise was performed as treadmill running (13.5m/min, 0% grade). Mice were OVA challenged repeatedly throughout the exercise protocol. At protocol completion, mice were analyzed for changes in the number and suppressive function of CD4(+)CD25(+)Foxp3(+) cells isolated from lungs, mediastinal lymph nodes, and spleens. Results show that exercise increased significantly the number of Foxp3(+) cells within the lungs and mediastinal lymph nodes, but not the spleens, of OVA-treated mice as compared with sedentary controls. Exercise also enhanced the suppression function of CD4(+)CD25(+)Foxp3(+) Treg cells derived from OVA-treated mice as compared with sedentary controls. Specifically, Treg cells from exercised, OVA-treated mice more effectively suppressed CD4(+)CD25(-) cell proliferation and Th2 cytokine production in vitro. Enhanced suppression was associated with increased protein levels of TGF-beta and lesser amounts of IL-10 and IL-17; however, blocking TGF-beta had no effect on suppressive functions. These data demonstrate that exercise-mediated increases in Treg cell function may play a role in the attenuation of airway inflammation. Further, these results indicate that moderate intensity aerobic exercise training may alter the Treg cell function within the asthmatic airway.
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Thomas
T
Lowder
Kari
K
Dugger
Jessy
J
Deshane
Kim
K
Estell
Lisa M
LM
Schwiebert
D000332:Aerobiosis / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015704:CD4 Antigens / Q000096:biosynthesis; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D010047:Ovalbumin