Frontiers in immunology
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Frontiers in immunology · Jan 2018
ReviewImmunothrombotic Activity of Damage-Associated Molecular Patterns and Extracellular Vesicles in Secondary Organ Failure Induced by Trauma and Sterile Insults.
Despite significant improvements in injury prevention and emergency response, injury-related death and morbidity continues to increase in the US and worldwide. Patients with trauma, invasive operations, anti-cancer treatment, and organ transplantation produce a host of danger signals and high levels of pro-inflammatory and pro-thrombotic mediators, such as damage-associated molecular patterns (DAMPs) and extracellular vesicles (EVs). DAMPs (e.g., nucleic acids, histone, high-mobility group box 1 protein, and S100) are molecules released from injured, stressed, or activated cells that act as endogenous ligands of innate immune receptors, whereas EVs (e.g., microparticle and exosome) are membranous vesicles budding off from plasma membranes and act as messengers between cells. ⋯ Blocking or neutralizing DAMPs using antibodies or small molecules has been demonstrated to ameliorate sepsis and SOF in animal models. Furthermore, a membrane immobilized with nucleic acid-binding polymers captured and removed multiple DAMPs and EVs from extracellular fluids, thereby preventing the onset of DAMP- and EV-induced inflammatory and thrombotic complications in vitro and in vivo. In this review, we will summarize the current state of knowledge of DAMPs, EVs, and SOF and discuss potential therapeutics and preventive intervention for organ failure secondary to trauma, surgery, anti-cancer therapy, and allogeneic transplantation.
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Frontiers in immunology · Jan 2018
ReviewNiches for the Long-Term Maintenance of Tissue-Resident Memory T Cells.
Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. ⋯ The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that maintain TRM cells in different tissues.
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Frontiers in immunology · Jan 2018
ReviewClustered Regularly Interspaced Short Palindromic Repeats/Cas9 Gene Editing Technique in Xenotransplantation.
Genetically modified pigs have been considered favorable resources in xenotransplantation. Microinjection of randomly integrating transgenes into zygotes, somatic cell nuclear transfer, homologous recombination, zinc finger nucleases, transcription activator-like effector nucleases, and most recently, clustered regularly interspaced short palindromic repeats-cas9 (CRISPR/Cas9) are the techniques that have been used to generate these animals. Here, we provide an overview of the CRISPR approaches that have been used to modify genes which are vital in improving xenograft survival rate, including cytidine monophosphate-N-acetylneuraminic acid hydroxylase, B1,4N-acetylgalactosaminyltransferase, isoglobotrihexosylceramide synthase, class I MHC, von Willebrand factor, C3, and porcine endogenous retroviruses. In addition, we will mention the importance of potential candidate genes which could be targeted using CRISPR/Cas9.
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Frontiers in immunology · Jan 2018
Low-Dose Mycophenolate Mofetil for Treatment of Neuromyelitis Optica Spectrum Disorders: A Prospective Multicenter Study in South China.
Objective: To evaluate the efficacy and safety of low-dose mycophenolate mofetil (MMF, 1,000 mg/day) treatment of neuromyelitis optica spectrum disorders (NMOSDs). Methods: This study was a multicenter, open, prospective, follow-up clinical trial. The data include retrospective clinical data from the pretreatment phase and prospective data from the post-treatment phase. ⋯ Fourteen (16%) of the total patients discontinued MMF after our last follow-up for various reasons and switched to azathioprine or rituximab. Conclusion: Low-dose MMF reduced clinical relapse and disability in NMOSD patients in South China. However, some patients still suffered from adverse events at this dosage.
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Frontiers in immunology · Jan 2018
The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus.
Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. ⋯ Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.