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This review provides an overview of evidence supporting the existence of distinct homeostatic and inflammatory eosinophil subpopulations in health and disease. Particular emphasis is placed on describing the phenotypic and functional roles of these eosinophil subtypes in asthma, as well as the phenotypic changes induced by clinical therapy with the anti-IL-5 biologic agent, mepolizumab. Improved understanding of distinct eosinophil phenotypes may enable targeting of select subpopulations in the treatment of patients with type 2 inflammatory diseases such as asthma. [ABSTRACT FROM AUTHOR]

This article, published in the journal Allergy, discusses a study that explores the existence of different subtypes of asthma based on immune signaling pathways. The study recruited 200 asthmatic patients and measured levels of certain cytokines in their sputum. The results revealed two distinct pathways of immune signaling, each associated with different patterns of cytokine expression. One pathway was linked to more severe disease and frequent hospitalizations. The study suggests that understanding these subtypes could lead to more targeted treatments for asthma. However, further research is needed to confirm these findings. The article also includes a table with various data points related to asthma patients, providing valuable information for research purposes. [Extracted from the article]

While Blankenship's rhetorical empathy offers a lot in terms of speaking across differences, it fails to deeply interrogate the examples it utilizes to shape a rhetorical empathy praxis. Blankenship is careful to outline how Addams comes to function as an example of rhetorical empathy to elucidate how rhetorical empathy operates as a praxis that becomes an "embodied identity" (p. 67). Building on her earlier assertions about storytelling and fostering rhetorical empathy, Blankenship argues for the importance of storytelling and personal experience in student writing. While she does not directly discuss WAC/WID theories, Blankenship's book discusses how to engage in rhetorical empathy within everyday contexts, which suggests the theory has a larger application and allows for a consideration of how rhetorical empathy informs pedagogical praxis. [Extracted from the article]

Globally, the COVID-19 pandemic has not only revealed medical disparities between countries in terms of access to vaccines but has also unveiled huge rifts in knowledge and information flow regarding the pandemic and vaccination amongst the general public. With this in view, we will interrogate how grassroot communicators and social networking sites have worked alongside each other to disseminate information about the pandemic that counters the narratives provided by the state. As scholars of rhetoric, we intend to trace the ways in which professional communication and state disinformation produce information vacuums amongst citizens while also illuminating how localized resistance and social justice activism taking place through coalition building on social media, can disrupt and dismantle deficiency narratives and furthermore provide grassroot material support to those in dire need. In other words, drawing upon Ding's Critical Contextualized Methodology, the proposed chapter will present a case study on Nepal by incorporating the petite narratives--after Lyotard--of "non-western cultural actors" (Ding, 2014, p. 30) in order to study the process and impact of alternative information flows during the time of risk and disaster, especially during the ongoing global pandemic. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 5 (IRF5) polymorphisms are strongly associated with an increased risk of developing the autoimmune disease systemic lupus erythematosus. In mouse lupus models, IRF5-deficiency was shown to reduce disease severity consistent with an important role for IRF5 in disease pathogenesis. However these mouse studies were confounded by the recent demonstration that the IRF5 knockout mouse line contained a loss-of-function mutation in the dedicator of cytokinesis 2 (DOCK2) gene. As DOCK2 regulates lymphocyte trafficking and Toll-like receptor signaling, this raised the possibility that some of the protective effects attributed to IRF5 deficiency in the mouse lupus models may instead have been due to DOCK2 deficiency. We have therefore here evaluated the effect of IRF5-deficiency in the MRL/lpr mouse lupus model in the absence of the DOCK2 mutation. We find that IRF5-deficient (IRF5−/−) MRL/lpr mice develop much less severe disease than their IRF5-sufficient (IRF5+/+) littermates. Despite markedly lower serum levels of anti-nuclear autoantibodies and reduced total splenocyte and CD4+ T cell numbers, IRF5−/− MRL/lpr mice have similar numbers of all splenic B cell subsets compared to IRF5+/+ MRL/lpr mice, suggesting that IRF5 is not involved in B cell development up to the mature B cell stage. However, IRF5−/− MRL/lpr mice have greatly reduced numbers of spleen plasmablasts and bone marrow plasma cells. Serum levels of B lymphocyte stimulator (BLyS) were markedly elevated in the MRL/lpr mice but no effect of IRF5 on serum BLyS levels was seen. Overall our data demonstrate that IRF5 contributes to disease pathogenesis in the MRL/lpr lupus model and that this is due, at least in part, to the role of IRF5 in plasma cell formation. Our data also suggest that combined therapy targeting both IRF5 and BLyS might be a particularly effective therapeutic approach in lupus. [ABSTRACT FROM AUTHOR]

Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE-/- mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients. [ABSTRACT FROM AUTHOR]

Intrauterine bacterial infections are a well-established cause of pregnancy complications. One key observation in a number of abnormal pregnancies is that placental apoptosis is significantly elevated. First trimester trophoblast cells are known to express TLR1 and TLR2 and to undergo apoptosis following exposure to Gram-positive bacterial peptidoglycan (PDG). Thus, the objectives of this study were to determine whether PDG-induced pregnancy complications are associated with placental apoptosis and to characterize the cellular mechanisms involved. We have demonstrated, using an animal model, that delivery of PDG to pregnant mice early in gestation resulted in highly elevated placental apoptosis, evidenced by trophoblast M-30 and active caspase 3 immunostaining. Using an in vitro model of human first trimester trophoblasts, apoptosis induced by PDG was found to be mediated by both TLR1 and TLR2 and that this could be blocked by the presence of TLR6. Furthermore, in the presence of TLR6, exposure to PDG resulted in trophoblast NF-kappaB activation and triggered these cells to secrete IL-8 and IL-6. The findings of this study suggest that a Gram-positive bacterial infection, through TLR2 and TLR1, may directly promote the elevated trophoblast cell death and that this may be the underlying mechanism of pregnancy complications, such as preterm delivery. Furthermore, the expression of TLR6 may be a key factor in determining whether the response to PDG would be apoptosis or inflammation.