Foxa2 is a member of the Forkhead family of nuclear transcription factors that is highly expressed in respiratory epithelial cells of the developing and mature lung. Foxa2 is required for normal airway epithelial differentiation, and its deletion causes goblet-cell metaplasia and Th2-mediated pulmonary inflammation during postnatal development. Foxa2 expression is inhibited during aeroallergen sensitization and after stimulation with Th2 cytokines, when its loss is associated with goblet-cell metaplasia. Mechanisms by which Foxa2 controls airway epithelial differentiation and Th2 immunity are incompletely known. During the first 2 weeks after birth, the loss of Foxa2 increases the production of leukotrienes (LTs) and Th2 cytokines in the lungs of Foxa2 gene-targeted mice. Foxa2 expression inhibited 15-lipoxygenase (Alox15) and increased Alox5 transcription, each encoding key lipoxygenases associated with asthma. The inhibition of the cysteinyl LT (CysLT) signaling pathway by montelukast inhibited IL-4, IL-5, eotaxin-2, and regulated upon activation normal T cell expressed and presumably secreted expression in the developing lungs of Foxa2 gene-targeted mice. Montelukast inhibited the expression of genes regulating mucus metaplasia, including Spdef, Muc5ac, Foxa3, and Arg2. Foxa2 plays a cell-autonomous role in the respiratory epithelium, and is required for the suppression of Th2 immunity and mucus metaplasia in the developing lung in a process determined in part by its regulation of the CysLT pathway.

We examine the stability and properties of three Au 21 cage structures, one with D 3 symmetry and denoted as Au 21 (D 3 ), which is novel, and the other two with C 2v symmetry. One, denoted as Au 21 (C 2v -1), has been previously reported but the other, denoted as Au 21 (C 2v -2), is novel. As reference Au 21 structures, we also examine a sheet isomer and a compact isomer, Au 21 (C s -Tetra), formed by adsorbing an Au atom on Au 20 (T d ).For all structures, we consider charge ranging from −1 to +4. For the Au 21 cage structures, a primary property of interest is their spherical aromaticity, as measured by their nucleus independent chemical shift. Our focus is on charge +3 since each gold atom is assumed to contribute one (6s) valence electron, and 18 is a magic number for shell closing. We find that, although Au 21 (D 3 ) +3 has the largest aromaticity, it is not the most stable Au + 3 21 cage species. Surprisingly, Au 21 (C 2v -2), which is not even stable as a neutral cage species, is the most stable tri-cation cage species. We also examine the stability of (neutral) Au 21 X n cage structures relative to Au 21 X n structures derived from Au 21 (C s -Tetra) (with X = F, Cl, Br, I and n = 1, 3, 5). We find that, although Au 21 F 3 derived from Au 21 (D 3 ) has the largest aromaticity, it is not the most stable Au 21 F 3 cage structure. Nonetheless, all cage structures are stabilized relative to Au 21 (C s -Tetra) and, remarkably, for the trichlorinated, tribrominated, and triiodineated clusters, at least one cage structure is more stable than its Au 21 (C s -Tetra) counterpart. K E Y W O R D S density functional theory, gold nanocluster, spherical aromaticity