Frequency Tunable, Cavity-Enhanced Single Erbium Quantum Emitter in the Telecom Band.

Single quantum emitters embedded in solid-state hosts are an ideal platform for realizing quantum information processors and quantum network nodes. Among the currently investigated candidates, Er^{3+} ions are particularly appealing due to their 1.5 µm optical transition in the telecom band as well as their long spin coherence times. However, the long lifetimes of the excited state-generally in excess of 1 ms-along with the inhomogeneous broadening of the optical transition result in significant challenges. Photon emission rates are prohibitively small, and different emitters generally create photons with distinct spectra, thereby preventing multiphoton interference-a requirement for building large-scale, multinode quantum networks. Here we solve this challenge by demonstrating for the first time linear Stark tuning of the emission frequency of a single Er^{3+} ion. Our ions are embedded in a lithium niobate crystal and couple evanescently to a silicon nanophotonic crystal cavity that provides a strong increase of the measured decay rate. By applying an electric field along the crystal c axis, we achieve a Stark tuning greater than the ion's linewidth without changing the single-photon emission statistics of the ion. These results are a key step towards rare earth ion-based quantum networks.

Constraints on nonlocality in networks from no-signaling and independence.

The possibility of Bell inequality violations in quantum theory had a profound impact on our understanding of the correlations that can be shared by distant parties. Generalizing the concept of Bell nonlocality to networks leads to novel forms of correlations, the characterization of which is, however, challenging. Here, we investigate constraints on correlations in networks under the natural assumptions of no-signaling and independence of the sources. We consider the triangle network with binary outputs, and derive strong constraints on correlations even though the parties receive no input, i.e., each party performs a fixed measurement. We show that some of these constraints are tight, by constructing explicit local models (i.e. where sources distribute classical variables) that can saturate them. However, we also observe that other constraints can apparently not be saturated by local models, which opens the possibility of having nonlocal (but non-signaling) correlations in the triangle network with binary outputs.

p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages.

The CDKN2A locus, which contains the tumor suppressor gene p16(INK4a), is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize toward classically (CAMϕ) or alternatively (AAMϕ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16(INK4a) deficiency (p16(-/-)) modulates the macrophage phenotype. Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16(-/-) BM displayed higher hepatic AAMϕ marker expression levels on Schistosoma mansoni infection, an in vivo model of AAMϕ phenotype skewing. Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,ß phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,ß. These findings identify p16(INK4a) as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases.

Eosinophil-derived IFN-gamma induces airway hyperresponsiveness and lung inflammation in the absence of lymphocytes.

BACKGROUND: Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site. OBJECTIVE: The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated. METHODS: Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients. RESULTS: Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil-induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism. CONCLUSIONS: These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine.

Fc(epsilon)RI and FcgammaRIII/CD16 differentially regulate atopic dermatitis in mice.

The high-affinity IgE receptor Fc(epsilon)RI and, in some models, the low-affinity IgG receptor Fc(epsilon)RIIII/CD16 play an essential role in allergic diseases. In human skin, they are present on APCs and effector cells recruited into the inflamed dermis. FcRgamma is a subunit shared, among other FcRs, by Fc(epsilon)RI and CD16 and is essential to their assembly and signal transduction. Using an experimental model reproducing some features of human atopic dermatitis and specific FcR-deficient mice, we have herein delineated the respective contribution of Fc(epsilon)RIand Fc(epsilon)RIII/CD16 to the pathology. We demonstrate that symptoms of atopic dermatitis are completely absent in FcRgamma-deficient animals but only partially inhibited in either Fc(epsilon)RI- or FcgammaRIII/CD16-deficient animals. Absence or attenuation of the pathology is correlated to increased skin expression of regulatory IL-10 and Foxp3. While Fc(epsilon)RI controls both Th1 and Th2 skin response, mast cell recruitment into draining lymph nodes and IgE production, CD16 regulates only Th2 skin response, as well as T cell proliferation and IgG1 production. This isotype-specific regulation by the cognate FcR is associated to a differential regulation of IL-4 and IL-21 expression in the draining lymph nodes. Fc(epsilon)RIand CD16 thus contribute to atopic dermatitis but differentially regulate immune responses associated with the disease. Targeting both IgE/Fc(epsilon)RI and IgG/CD16 interactions might represent an efficient therapeutic strategy for allergic diseases.

Peroxisome proliferator-activated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis.

BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. In addition to their regulatory role on lipid and glucose metabolism, they exert anti-inflammatory properties. In skin both PPAR-alpha and PPAR-beta/delta regulate keratinocyte proliferation/differentiation and contribute to wound healing. The 3 PPAR isoforms are expressed by several cell types recruited into the dermis during inflammation. OBJECTIVE: We have investigated the role of PPAR-alpha in the regulation of atopic dermatitis (AD), a common skin inflammatory disease. METHODS: We chose a mouse model of inflammatory dermatosis with immunologic features of AD and used epicutaneous sensitization with ovalbumin in the absence of adjuvant, which mimics the human pathology. RESULTS: On antigen sensitization, PPAR-alpha-deficient mice display increased epidermal thickening, dermal recruitment of inflammatory cells, lung inflammation, airway hyperresponsiveness, and IgE and IgG2a production compared with their wild-type counterparts. Increased inflammation was correlated to an enhancement of TH2 and, to a greater extent, TH1 responses and to increased skin expression of nuclear factor kappaB. Interestingly, PPAR-alpha expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-alpha expression might contribute to the pathology. Topical application of WY14643, a specific PPAR-alpha agonist, significantly decreased antigen-induced skin inflammation in the AD model. CONCLUSION: PPAR-alpha acts as a negative regulator of skin inflammation in AD.