Springer Science and Business Media LLC

The intestinal mucosa is densely packed with antibody-secreting B cells, the majority of which produce IgA. Mucosal antibodies have traditionally been thought of as neutralizing antibodies that exclude antigens, but they also function in antigen sampling, allowing for selective transcytosis of antigens from the intestinal lumen. IgE-mediated antigen uptake can facilitate the development of allergic reactions to foods, but emerging evidence indicates that IgG-mediated antigen uptake may also play an important role in the development of immune tolerance to foods, particularly in the neonate. This review will focus on the role of intestinal immunoglobulins in the development of clinical tolerance and allergy to food antigens.

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.

Ischemic stroke (IS) is the leading cause of acquired disability and the second leading cause of dementia and mortality. Current treatments for IS are primarily focused on revascularization of the occluded artery. However, only 10% of patients are eligible for revascularization and 50% of revascularized patients remain disabled at 3 months. Accumulating evidence highlight the prognostic significance of the neuro- and thrombo-inflammatory response after IS. However, several randomized trials of promising immunosuppressive or immunomodulatory drugs failed to show positive results. Insufficient understanding of inter-patient variability in the cellular, functional, and spatial organization of the inflammatory response to IS likely contributed to the failure to translate preclinical findings into successful clinical trials. The inflammatory response to IS involves complex interactions between neuronal, glial, and immune cell subsets across multiple immunological compartments, including the blood-brain barrier, the meningeal lymphatic vessels, the choroid plexus, and the skull bone marrow. Here, we review the neuro- and thrombo-inflammatory responses to IS. We discuss how clinical imaging and single-cell omic technologies have refined our understanding of the spatial organization of pathobiological processes driving clinical outcomes in patients with an IS. We also introduce recent developments in machine learning statistical methods for the integration of multi-omic data (biological and radiological) to identify patient-specific inflammatory states predictive of IS clinical outcomes.

The members of the NOX/DUOX family of NADPH oxidases mediate such physiologic functions as host defense, cell signaling, and thyroid hormone biosynthesis through the generation of reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide. Moreover, ROS are involved in a broad range of fundamental biochemical and cellular processes, and data accumulated in recent years indicate that the NOX enzymes comprise one of the most important biological sources of ROS. Given the high biochemical reactivity of ROS, it is not surprising that they have been implicated in a wide variety of pathologies and diseases. Prominent among the settings that feature ROS-mediated tissue injury are disorders associated with inflammation, aging, and progressive degenerative changes in cells and organ systems, and it appears that essentially no organ system is exempt. Among the disorders currently believed to be mediated at least in part by NOX-derived ROS are hypertension, aortic aneurysm, myocardial infarction (and other ischemia–reperfusion disorders), pulmonary fibrosis and hypertension, amyotropic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, ischemic stroke, diabetic nephropathy, and renal cell carcinoma. Several small-molecule and peptide inhibitors of the NOX enzymes have been useful in experimental studies, but issues of specificity, potency, and toxicity militate against any of the existing published compounds as candidates for drug development. Given the broad array of disease targets documented in recent work, the time is here for vigorous efforts to develop clinically useful inhibitors of the NOX enzymes. As most (though not all) NOX-related diseases appear to be mediated by a single member of the NOX family, agents with isoform specificity will be preferred, although broadly active NOX inhibitors may prove to be useful in some settings.

Pluripotent stem cells hold great promises for regenerative medicine. They might become useful as a universal source for a battery of new cell replacement therapies. Among the major concerns for the clinical application of stem cell-derived grafts are the risks of immune rejection and tumor formation. Pluripotency and tumorigenicity are closely linked features of pluripotent stem cells. However, the capacity to form teratomas or other tumors is not sufficiently described by inherited features of a stem cell line or a stem cell-derived graft. The tumorigenicity always depends on the inability of the recipient to reject the tumorigenic cells. This review summarizes recent data on the tumorigenicity of pluripotent stem cells in immunodeficient, syngeneic, allogeneic, and xenogeneic hosts. The effects of immunosuppressive treatment and cell differentiation are discussed. Different immune effector mechanisms appear to be involved in the rejection of undifferentiated and differentiated cell populations. Elements of the innate immune system, such as natural killer cells and the complement system, which are active also in syngeneic recipients, appear to preferentially reject undifferentiated cells. This effect could reduce the risk of tumor formation in immunocompetent recipients. Cell differentiation apparently increases susceptibility to rejection by the adaptive immune system in allogeneic hosts. The current data suggest that the immune system of the recipient has a major impact on the outcome of pluripotent stem cell transplantation, whether it is rejection, engraftment, or tumor development. This has to be considered when the results of experimental transplantation models are interpreted and even more when translation into clinics is planned.