IL-17A produced by αß T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.

Emerging evidence suggests that the T helper 17 (T(H)17) subset of αß T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvß8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvß8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle.

Long-term stable canine mandibular augmentation using autologous bone marrow stromal cells and hydroxyapatite/tricalcium phosphate.

Transplants of culture-expanded bone marrow stromal cells (BMSCs) combined with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds successfully form cortico-cancellous bone to reconstruct the dog craniofacial skeleton. Yet, these transplants' long-term stability in large animal models has not been evaluated. This study's purpose was the evaluation of long-term BMSC transplant stability when used to augment the mandible. Here, autologous BMSC-HA/TCP transplants were introduced onto the unilateral dog mandible as onlay grafts, while contralateral control mandibles received HA/TCP onlays alone. Quantitative CT (qCT) scans were obtained both early and late after transplantation. Transplants were harvested up to 19 months later for histologic and mechanical analyses. In all dogs, BMSC transplants formed significantly greater amounts of bone over their control counterparts. The new bone formed an extensive union with the underlying mandible. BMSC transplants retained the majority of their initial volume, while control (HA/TCP only) transplants were nearly completely resorbed. By qCT, the extent of newly formed bone could be determined non-invasively. In summary, HA/TCP particles alone undergo a high degree of resorption, while autologous cultured BMSC-HA/TCP transplants provide long-term bony augmentation of the mandible.