Forum on immunopathological diseases and therapeutics最新文献

The Krüppel-like factor 4 (KLF4) gene is located on chromosome 9q31. All of the currently known 17 KLF transcription regulators that have similarity with members of the specificity protein family are distinctly characterized by the Cys₂/His₂ zinc finger motifs at their carboxyl terminals for preferential binding to the GC/GT box or the CACCC element of the gene promoter and enhancer regions. KLF4 is a transcriptional regulator of cell proliferation, differentiation, apoptosis, migration, and invasion, emphasizing its importance in diagnosis and prognosis of particular tumors. KLF4 has been implicated in tumor progression as well as in tumor suppression, depending on tumor types and contexts. Different studies so far strongly suggest that KLF4 acts as an oncogene in glioblastoma, which is the most malignant and prevalent brain tumor in human adult. It is now well established that the presence of glioblastoma stem cells (GSCs) in glioblastoma causes therapy resistance and progressive growth of the tumor. Because KLF4 is one of the key stemness factors in GSCs, it is likely that KLF4 contributes significantly to the survival of GSCs and the recurrence of glioblastoma. On the other hand, recent studies show that KLF4 can act as a tumor suppressor in human malignant neuroblastoma, which is a deadly tumor mostly in children, by inhibiting the cell cycle and activating the cell differentiation and death pathways. Our increasing understanding of the molecular mechanisms of the contrasting roles of KLF4 in glioblastoma and neuroblastoma is useful for superior diagnosis, therapy, and prognosis of these tumors of the nervous system.

Premature infants are at increased risk for morbidity and mortality due to necrotizing enterocolitis (NEC) and sepsis. Probiotics decrease the risk of NEC and death in premature infants; however, mechanisms of action are unclear. A wide variety of probiotic species have been evaluated for potential beneficial properties in vitro, in animal models, and in clinical trials of premature infants. Although there is variation by species and even strain, common mechanisms of protection include attenuation of intestinal inflammation, apoptosis, dysmotility, permeability, supplanting other gut microbes through production of bacteriocins, and more effective use of available nutrients. Here, we review the most promising probiotics and what is known about their impact on the innate and adaptive immune response.

Borrelia burgdorferi is the causative bacterial agent of Lyme disease, the most prevalent tick-borne infection in North America. The ability of B. burgdorferi to cause disease is highly dependent on its capacity to evade the immune response during infection of the mammalian host. One of the ways in which B. burgdorferi is known to evade the immune response is antigenic variation of the variable major protein (VMP)-like sequence (Vls) E lipoprotein. Past research involving the B. burgdorferi antigenic variation system has implicated a gene-conversion mechanism for vlsE recombination, analyzed the long-term dynamic changes occurring within VlsE, and established the critical importance of antigenic variation for persistent infection of the mammalian host. However, a role for the VlsE protein other than providing an antigenic disguise is currently unknown, but it has been proposed that the protein may function in other forms of immune evasion. Although a substantial number of additional proteins reside on the bacterial surface, VlsE is the only known antigen that exhibits ongoing variation of its surface epitopes. This suggests that B. burgdorferi may use a VlsE-mediated system for immune avoidance of its surface antigens. Several recent experimental studies involving host reinfection, superinfection, and the importance of VlsE antigenic variation during the pathogen's enzootic cycle have been used to address this question. Here, the cumulative results from these studies are reviewed, and the knowledge gaps that remain regarding the role of VlsE for immune avoidance are discussed.

The introduction of immunopathologic reaction classification in the 1960s led to a major advance in understanding immune effector mechanisms and how lesions of immunopathologic diseases developed. In this article, immunopathologic mechanisms are presented for experimental models of syphilis, influenza, and asthma. The chancre of syphilis is a delayed hypersensitivity skin reaction that is initiated by sensitized T cells that activate macrophages to phagocytose and kill the infecting organism, Treponema pallidum, in interstitial tissues. The primary immune effector mechanism in experimental influenza is T-cell-mediated cytotoxicity that kills infected epithelial cells, bronchial lining cells, and Type-II pneumocytes, in a manner similar to viral exanthema. The bronchial lesions of the experimental model of asthma in mice are preceded by an immune complex vasculitis and not an immunoglobulin E-mediated mast cell mechanism.

Chlamydia pneumoniae, an obligate intracellular bacterial pathogen, has long been investigated as a potential developmental or exacerbating factor in various pathologies. Its unique lifestyle and ability to disseminate throughout the host while persisting in relative safety from the immune response has placed this obligate intracellular pathogen in the crosshairs as a potentially mitigating factor in chronic inflammatory diseases. Many animal model and human correlative studies have been performed to confirm or deny a role for C. pneumoniae infection in these disorders. In some cases, antibiotic clinical trials were conducted to prove a link between bacterial infections and atherosclerosis. In this review, we detail the latest information regarding the potential role that C. pneumoniae infection may have in chronic inflammatory diseases.