A role for beta-2 adrenergic receptors in the moderate aerobic exercise-modulated T regulatory cell function within a murine OVA-driven allergic asthmatic lung (HYP7P.287)

We have shown moderate aerobic exercise can increase both the number and function of T regulatory (TREG) cells that suppress Th2 responses of an ovalbumin (OVA)-driven murine asthma model by an unknown mechanism. Exercise can communicate with TREG cells with the systemic release of catecholamines that bind to Beta-2-adrenergic receptors (β2-AR) and generate cAMP signals that can affect cell function. In these studies, we investigated a role for β2-AR in the exercise-mediated modulation of TREG cell function. For these studies, TREG cells (CD4+CD25+) were depleted from female BALB/cJ mice by i.v. injection of anti-CD25. Either 500,000 wt or β2-AR-/- TREG cells were adoptively transferred into the TREG-depleted BALB/cJ mice. Mice were sensitized/challenged with OVA to mimic allergic asthma pathogenesis. Mice were moderately exercised 45 min post-OVA challenge on a treadmill for 1hr 3x/wk for 4wks. Upon protocol completion, mice were examined for changes in TREG cell suppressive function and their resulting TREG cAMP levels. Our results show that exercise increases TREG function in vitro as compared with sedentary controls. However, the increase in TREG function of exercised TREG cells was abrogated in the absence of β2-ARs. We conclude that moderate aerobic exercise attenuates asthma-related airway inflammation via a mechanism that involves increased TREG cell function modulated by their expression of β2-ARs and subsequent production of cAMP.