Site-Specific Effects of Swimming on Bone Density in Female Collegiate Swimmers

International Journal of Exercise Science 13(1): 249-259, 2020. While swimming provides numerous cardiovascular and overall health benefits, past research suggests it provides no constructive benefits to bone strength and density at dual energy x-ray absorptiometry (DXA) measured hip and lumbar spine sites when compared to sedentary individuals. However, little research has focused on skeletal sites stressed by muscle forces during swimming such as the humerus, hip, and radius. The purpose of this study was to investigatesite-specific bone strength adaptations among female collegiate swimmers compared to sedentary controls. Bone geometry and strength were assessed by DXA and peripheral quantitative computed tomography (pQCT) in ten female collegiate swimmers and ten sedentary controls (\u3c150 minutes/week of moderate-to-vigorous physical activity) ages 18-23 years. There were no significant differences between groups in the DXA-derived outcomes. Among pQCT-measured sites, the control group had a 14.8% greater bone cortical area and 6.1% greater cortical volumetric density compared to swimmers (both p\u3c0.05) at the proximal tibia (66%) site. Hip structural analysis was also performed to observe the strength and loading power at the narrowest part of the proximal femur, but no significant differences were found between groups. With no significant bone density or strength differences between groups at the humerus, radius, or distal tibia sites, this research suggests that swimming may not have osteogenic benefits, even at site-specific locations commonly stressed during the sport. For overall health, these results suggest that swimming should be supplemented with weight-bearing and resistance exercises to preserve bone strength and prevent deterioration of bone as one ages

REV-ERBα regulates T(H)17 cell development and autoimmunity

ROR gamma t is well recognized as the lineage-defining transcription factor for T helper 17 (T(H)17) cell development. However, the cell-intrinsic mechanisms that negatively regulate T(H)17 cell development and autoimmunity remain poorly understood. Here, we demonstrate that the transcriptional repressor REV-ERB alpha is exclusively expressed in T(H)17 cells, competes with ROR gamma t for their shared DNA consensus sequence, and negatively regulates T(H)17 cell development via repression of genes traditionally characterized as ROR gamma t dependent, including parallel to 17a. Deletion of REV-ERB alpha enhanced T(H)17-mediated pro-inflammatory cytokine expression, exacerbating experimental autoimmune encephalomyelitis (EAE) and colitis. Treatment with REV-ERB-specific synthetic ligands, which have similar phenotypic properties as ROR gamma modulators, suppressed T(H)17 cell development, was effective in colitis intervention studies, and significantly decreased the onset, severity, and relapse rate in several models of EAE without affecting thymic cellularity. Our results establish that REV-ERB alpha negatively regulates pro-inflammatory T(H)17 responses in vivo and identifies the REV-ERBs as potential targets for the treatment of T(H)17-mediated autoimmune diseases

CAR directs T cell adaptation to bile acids in the small intestine

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn's disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mouse small intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1-/- or Rag2-/- mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn's disease and defines lymphocyte sub-specialization in the small intestine