IL-4–Stat6 Signaling Induces Tristetraprolin Expression and Inhibits TNF-α Production in Mast Cells

Increasing evidence has revealed that mast cell–derived tumor necrosis factor α (TNF-α) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF-α production in mast cells. IL-4 inhibited immunoglobulin E–induced TNF-α production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)–deficient mice. IL-4 also inhibited TNF-α production in cultured mast cells by a Stat6-dependent mechanism. IL-4–Stat6 signaling induced TNF-α mRNA destabilization in an AU-rich element (ARE)–dependent manner, but did not affect TNF-α promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4–induced down-regulation of TNF-α production in mast cells. These results suggest that IL-4–Stat6 signaling induces TTP expression and, thus, destabilizes TNF-α mRNA in an ARE-dependent manner

Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22

The interleukin (IL) 17 family of cytokines has emerged to be critical for host defense as well as the pathogenesis of autoimmune and autoinflammatory disorders, and serves to link adaptive and innate responses. Recent studies have identified a new subset of T cells that selectively produce IL-17 (Th17 cells; Bettelli, E., T. Korn, and V.K. Kuchroo. 2007. Curr. Opin. Immunol. 19:652–657; Kolls, J.K., and A. Linden. 2004. Immunity. 21:467–476), but the regulation of IL-17 production by innate immune cells is less well understood. We report that in vitro stimulation with IL-23 induced IL-17 production by recombination activating gene (Rag) 2−/− splenocytes but not Rag2−/− common γ chain−/− splenocytes. We found that a major source of IL-17 was CD4+CD3−NK1.1−CD11b−Gr1−CD11c−B220− cells, a phenotype that corresponds to lymphoid tissue inducer–like cells (LTi-like cells), which constitutively expressed the IL-23 receptor, aryl hydrocarbon receptor, and CCR6. In vivo challenge with the yeast cell wall product zymosan rapidly induced IL-17 production in these cells. Genetic deletion of signal transducer and activator of transcription 3 reduced but did not abrogate IL-17 production in LTi-like cells. Thus, it appears that splenic LTi-like cells are a rapid source of IL-17 and IL-22, which might contribute to dynamic organization of secondary lymphoid organ structure or host defense

Transmission electron microscopy of topochemical conversion interface between La2Ti2O7 reactive template and perovskite product Li(0.16)LA(0.62)TiO(3) electrolyte

The topochemical conversion interface between a layered perovskite La2Ti2O7 and an ordered regular perovskite Li0.16La0.62TiO3, (LLTO) electrolyte was investigated using high-resolution transmission electron microscopy and scanning-transmission electron microscopy (STEM) for platelike La2Ti2O7 particles semi-reacted (at 1273 K) with the complementary reactants Li4Ti5O12 and TiO2. High-temperature X-ray diffraction analysis confirmed that regular perovskite-type product was formed in situ at 1173 K and above without the formation of any intermediate phases. The crystallographic relationship between the product and the template at the interface was determined by selected area electron diffraction to be orthorhombic LLTO [001](110) || monoclinic La2Ti2O7 [001](100). STEM revealed that the alternating La-rich and La-poor planes in the LLTO phase were aligned perpendicular to the interface, which was parallel to the interlayers, i.e., the (200) planes of the La2Ti2O7 template. At the interface, a unit-cell-thick La2Ti2O7 or a block of four-layered TiO6 octahedra between two interlayers is a basic unit converted into a regular perovskite-type product by shifting the block with La along the c-axis. This microscopic observation of the interface suggests the possibility of designing domain structures with improved ionic conductivity