Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity.

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.

Extracting more light for vertical emission: high power continuous wave operation of 1.3-µm quantum-dot photonic-crystal surface-emitting laser based on a flat band.

For long distance optical interconnects, 1.3-µm surface-emitting lasers are key devices. However, the low output power of several milliwatts limits their application. In this study, by introducing a two-dimensional photonic-crystal and using InAs quantum dots as active materials, a continuous-wave, 13.3-mW output power, 1.3-µm wavelength, room-temperature surface-emitting laser is achieved. In addition, such a device can be operated at high temperatures of up to 90 °C. The enhanced output power results from the flat band structure of the photonic crystal and an extra feedback mechanism. Surface emission is realized by photonic crystal diffraction and thus the distributed Bragg reflector is eliminated. The proposed device provides a means to overcome the limitations of low-power 1.3-µm surface-emitting lasers and increase the number of applications thereof.

Enhancing Third- and Fifth-Order Nonlinearity via Tunneling in Multiple Quantum Dots.

The nonlinearity of semiconductor quantum dots under the condition of low light levels has many important applications. In this study, linear absorption, self-Kerr nonlinearity, fifth-order nonlinearity and cross-Kerr nonlinearity of multiple quantum dots, which are coupled by multiple tunneling, are investigated by using the probability amplitude method. It is found that the linear and nonlinear properties of multiple quantum dots can be modified by the tunneling intensity and energy splitting of the system. Most importantly, it is possible to realize enhanced self-Kerr nonlinearity, fifth-order nonlinearity and cross-Kerr nonlinearity with low linear absorption by choosing suitable parameters for the multiple quantum dots. These results have many potential applications in nonlinear optics and quantum information devices using semiconductor quantum dots.

Parity-time symmetry in coherent asymmetric double quantum wells.

A coherently prepared asymmetric double semiconductor quantum well (QW) is proposed to realize parity-time (PT) symmetry. By appropriately tuning the laser fields and the pertinent QW parameters, PT-symmetric optical potentials are obtained by three different methods. Such a coherent QW system is reconfigurable and controllable, and it can generate new approaches of theoretically and experimentally studying PT-symmetric phenomena.

Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1-NF-κB Pathway.

Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1ß. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1-NF-κB pathway.