Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion

A determination of the molar gas constant R by acoustic thermometry in helium

We have determined the acoustic and microwave frequencies of a misaligned spherical resonator maintained near the temperature of the triple point of water and filled with helium with carefully characterized molar mass M = (4.002 6032 ± 0.000 0015) g mol-1, with a relative standard uncertainty ur(M) = 0.37×10-6. From these data and traceable thermometry we estimate the speed of sound in our sample of helium at TTPW = 273.16 K and zero pressure to be u0 2 = (945 710.45 ± 0.85) m2 s-2 and correspondingly deduce the value R = (8.314 4743 ± 0.000 0088) J mol-1 K-1 for the molar gas constant. We estimate the value k = R/NA = (1.380 6508 ± 0.000 0015) × 10-23 J K-1 for the Boltzmann constant using the currently accepted value of the Avogadro constant NA. These estimates of R and k, with a relative standard uncertainty of 1.06 × 10-6, are 1.47 parts in 106 above the values recommended by CODATA in 2010