Neutrophils might link intestinal damage to retinopathy in type 2 diabetes mellitus
Related Articles
Neutrophils in cancer: from biology to therapy
The view of neutrophils has shifted from simple phagocytic cells, whose main function is to kill pathogens, to very complex cells that are also involved in immune regulation and tissue repair. These cells are essential for maintaining and regaining tissue homeostasis. Neutrophils can be viewed as double-edged swords in a range of situations. The potent killing machinery necessary for immune responses to pathogens can easily lead to collateral damage to host tissues when inappropriately controlled. Furthermore, some subtypes of neutrophils are potent pathogen killers, whereas others are immunosuppressive or can aid in tissue healing. Finally, in tumor immunology, many examples of both protumorigenic and antitumorigenic properties of neutrophils have been described. This has important consequences for cancer therapy, as targeting neutrophils can lead to either suppressed or stimulated antitumor responses. This review will discuss the current knowledge regarding the pro- and antitumorigenic roles of neutrophils, leading to the concept of a confused state of neutrophil-driven pro-/antitumor responses.
The impact of aging on neutrophil functions and the contribution to periodontitis
The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils’ chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.
Intestinal epithelium in early life
Rapid development of the fetal and neonatal intestine is required to meet the growth requirements of early life and form a protective barrier against external insults encountered by the intestinal mucosa. The fetus receives nutrition via the placenta and is protected from harmful pathogens in utero, which leads to intestinal development in a relatively quiescent environment. Upon delivery, the intestinal mucosa is suddenly tasked with providing host defense and meeting nutritional demands. To serve these functions, an array of specialized epithelial cells develop from intestinal stem cells starting in utero and continuing postnatally. Intestinal disease results when these homeostatic processes are interrupted. For preterm neonates, the most common pathology resulting from epithelial barrier dysfunction is necrotizing enterocolitis (NEC). In this review, we discuss the normal development and function of the intestinal epithelium in early life as well as how disruption of these processes can lead to NEC.
Regulation of intestinal immunity by dietary fatty acids
Dietary fatty acids are absorbed through the intestine and are fundamental for cellular energy provision and structural formation. Dietary fatty acids profoundly affect intestinal immunity and influence the development and progression of inflammatory bowel disease, intestinal infections and tumors. Although different types of fatty acids exert differential roles in intestinal immunity, a western diet, rich in saturated fatty acids with abundant carbohydrates and studied as high-fat diet (HFD) in animal experiments, disturbs intestinal homeostasis and plays a pathogenic role in intestinal inflammatory diseases. Here, we review recent findings on the regulation of intestinal immunity by dietary fatty acids, focusing on HFD. We summarize HFD-altered immune responses leading to susceptibility to intestinal pathology and dissect the mechanisms involving the impact of HFD on immune cells, intestinal epithelial cells and the microbiota. Understanding the perturbation of intestinal immunity by HFD will provide new strategies for prevention and treatment of intestinal inflammatory diseases.
Interleukin-10 regulates goblet cell numbers through Notch signaling in the developing zebrafish intestine
Cytokines are immunomodulatory proteins that orchestrate cellular networks in health and disease. Among these, interleukin (IL)-10 is critical for the establishment of intestinal homeostasis, as mutations in components of the IL-10 signaling pathway result in spontaneous colitis. Whether IL-10 plays other than immunomodulatory roles in the intestines is poorly understood. Here, we report that il10, il10ra, and il10rb are expressed in the zebrafish developing intestine as early as 3 days post fertilization. CRISPR/Cas9-generated il10-deficient zebrafish larvae showed an increased expression of pro-inflammatory genes and an increased number of intestinal goblet cells compared to WT larvae. Mechanistically, Il10 promotes Notch signaling in zebrafish intestinal epithelial cells, which in turn restricts goblet cell expansion. Using murine organoids, we showed that IL-10 modulates goblet cell frequencies in mammals, suggesting conservation across species. This study demonstrates a previously unappreciated IL-10-Notch axis regulating goblet cell homeostasis in the developing zebrafish intestine and may help explain the disease severity of IL-10 deficiency in the intestines of mammals.
Responses