Following the Nonthermal Phase Transition in Niobium Dioxide by Time-Resolved Harmonic Spectroscopy.

Photoinduced phase transitions in correlated materials promise diverse applications from ultrafast switches to optoelectronics. Resolving those transitions and possible metastable phases temporally are key enablers for these applications, but challenge existing experimental approaches. Extreme nonlinear optics can help probe phase changes, as higher-order nonlinearities have higher sensitivity and temporal resolution to band structure and lattice deformations. Here the ultrafast transition from the semiconducting to the metallic phases in polycrystalline thin-film NbO_{2} is investigated by time-resolved harmonic spectroscopy. The emission strength of all harmonic orders shows a steplike suppression when the excitation fluence exceeds a threshold (∼11-12 mJ/cm^{2}), below the fluence required for the thermal transition-a signature of the nonthermal emergence of a metallic phase within 100±20 fs. This observation is backed by full ab initio simulations as well as a 1D chain model of high-harmonic generation from both phases. Our results demonstrate femtosecond harmonic probing of phase transitions and nonthermal dynamics in solids.

Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis.

We explored the possibility that pulsed antigen-presenting cells (APC) provide a model vector system for site-specific delivery of immunosuppressive proteins during collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. Thus, mice were treated with either B cells or macrophages engineered to secrete IL-4 and loaded (or not) with type II collagen (CII). Systemic injection of an IL-4-producing B cell hybridoma resulted in a reduction of arthritis severity which was further improved when APC were incubated with CII before their transfer. Unmanipulated B cells loaded with CII also exerted a potent suppressive effect. Likely, clinical amelioration was observed in mice given at priming syngeneic bone marrow-derived macrophages producing IL-4 and pulsed with CII in comparison to the other groups. When the same dose of cells was transferred at disease onset, a moderate beneficial effect was observed. Whatever the APC inoculated, the beneficial effect did not rely upon an IL-4-driven shift towards Th2 phenotype. Systemic administration of fluorescent dye labeled macrophages to arthritic mice has shown that some of these cells rapidly migrate to joints. Moreover, IL-4 transfected macrophages retained their potent capacity to present CII peptides to T cells. These findings validate the use of CII peptide-loaded engineered APC as therapeutic vector cells in CIA and allow consideration of this strategy for the administration of various anti-inflammatory proteins.

The type II decoy receptor of IL-1 inhibits murine collagen-induced arthritis.

IL-1 is a key cytokine involved in the inflammatory response. The type II receptor of IL-1 (IL-1RII) acts as a decoy receptor, binding and inhibiting the effect of IL-1. This study was undertaken to establish whether IL-1RII can ameliorate collagen-induced arthritis, a model of inflammatory arthritis in mice. We used human keratinocytes transfected with the human (h)IL-1 RII gene as a source of hIL-1 RII protein. We showed that these cells expressed both the membrane and soluble form of receptor. In vitro, IL-1-stimulated murine macrophage cells showed a decreased expression of TNF-alpha in the presence of hIL-1 RII. We engrafted the hIL-1RII-transfected cells in the back of mice developing collagen-induced arthritis. We found that clinical and histological parameters of arthritis were significantly decreased in mice treated with cells producing hIL-1RII. In addition, hIL-1RII administration was able to reduce the expression of mRNA for IL-6 and myeloperoxidase in the joints of treated animals. These data show that hIL-1 RII anti-inflammatory properties in the model of collagen-induced arthritis in mice and could have a regulatory role in rheumatoid arthritis.

Expression of Fas ligand improves the effect of IL-4 in collagen-induced arthritis.

The present study was aimed at investigating whether the expression of Fas ligand (FasL) by CHO cells transfected with IL-4 (CHO/IL-4) or IL-10 (CHO/IL-10) genes would improve the effect of the cytokine. DBA/ 1 mice immunized with type II collagen were treated with suboptimal doses of transfected CHO cells (a single s. c. injection of 2 x 10(5) cells) around onset of arthritis. Severe collagen-induced arthritis (CIA) developed in the control groups injected with PBS, CHO /beta-galactosidase/FasL, CHO/IL-4 or CHO/IL-10 cells. In contrast, administration of CHO/IL-4/FasL, but not CHO/IL-10/FasL, cells significantly reduced the clinical severity and resulted in rapid and sustained suppressive effect. Amelioration of CIA was not due to a prolonged in vivo secretion of IL-4 since expression of FasL by CHO cells shortened the in vivo survival of the xenogeneic cells. In fact, administration of FasL(+) cells was associated with a decreased proportion of Mac1(+) neutrophils in the blood and an increased expression of myeloperoxidase at the site of engineered cell engraftment. These findings suggest that the mechanism underlying the beneficial effect of IL-4 delivered by cells expressing FasL involves the combination of the anti-inflammatory properties of IL-4 and the apoptosis of Fas(+) Mac1(+) granulocytes participating in the pathogenic process.