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The latest study associating periodontitis and diabetes uncovers fresh perspectives on cellular-level immune alterations BUSAN, South Korea, Feb. 16, 2024 /PRNewswire/ -- Periodontitis (PD) is a common complication in individuals with diabetes mellitus (DM). Despite the profound implications for overall health, the complex bidirectional relationship between them lacks a comprehensive understanding so far, leaving the precise nature of their immunological connection inadequately understood. Prior studies focusing on local immune responses in gingival tissue fall short in capturing the systemic immunological relationship. Continue Reading The study associating periodontitis (PD) and diabetes mellitus (DM) using single-cell RNA analysis offers the first immunological explanation, revealing altered immune cell function and suggesting PD as a potential precursor to DM through the RESISTIN pathway. In an innovative study, researchers from the Republic of Korea have investigated the relationship between periodontitis (PD) and diabetes mellitus (DM). Led by Assistant Professor Yun Hak Kim from Pusan National University, the study employs pioneering single-cell RNA analysis and digs into the immune dynamics at the cellular level. This recent study was made available online on December 11, 2023, and was published in Volume 13, Issue 12 of the Clinical and Translational Medicine journal in December 2023. Dr. Kim says, "Our study promises to transform our understanding of the complex interplay between these two prevalent health conditions and sheds light on the systemic impact of these conditions, offering a potential avenue for targeted interventions." But what exactly is this immunological link? The study, conducted on a diverse group that included healthy individuals as well as patients with periodontitis (PD) and those with both PD and type 2 diabetes mellitus (PDDM), utilized single-cell RNA sequencing to explore the systemic immunological connections between PD and DM. The researchers methodically analyzed peripheral blood mononuclear cells by single cell RNA sequencing, revealing transcriptomic characteristics and cell interactions. The study identified pro-inflammatory cytokines rise in classical monocytes in both PD and PDDM groups. Further analysis revealed the influence of DM on T lymphocyte counts. CD4+ effector T cells exhibited reduced activation under DM conditions, indicating a broader systemic impact on immune regulation. The compromised functions of CD8+ T cells and natural killer (NK) cells in the presence of both PD and DM further highlight the intricate immune changes occurring at the cellular level. The RESISTIN pathway, known for its association with insulin resistance, was found to be intensified in both PD and PDDM groups, primarily involving classical monocytes. This discovery adds a crucial piece to the puzzle, suggesting a shared intercellular pathway that contributes to the complex PD-DM relationship. The discovery of RESISTIN in the blood of patients with periodontitis but without underlying diseases highlights its role in inflammation and its potential as a therapeutic target to reduce diabetes risk in patients with PD. The outcomes point to significant immune alterations in patients with both PD and DM, emphasizing the potential role of PD as a precursor to diabetes. In conclusion, this groundbreaking research provides a first-of-its-kind immunological explanation for the complex association between periodontitis and type 2 diabetes mellitus. The use of single-cell RNA analysis has uncovered cellular-level immune changes, offering a new perspective on the systemic impact of these prevalent health conditions. The study not only advances our scientific understanding but also lays the foundation for potential interventions aimed at diminishing the risk and impact of diabetes in individuals with periodontitis! Reference Title of original paper: Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis Journal: Clinical and Translational Medicine DOI: About Pusan National University Website: Media contact: Jae-Eun Lee [email protected] 82 51 510 7928 SOURCE Pusan National University

Using a mouse model of high fat diet-induced obesity, a team of scientists has found that, compared to males, female mice are protected against obesity and inflammation because they secrete more of an immune protein called RELMalpha. Associated with poorer mental health outcomes and reduced quality of life, obesity is on the rise in the United States. Currently, more than 30% of American adults are classified as obese. A risk factor for several diseases, including diabetes, cardiovascular disease, and COVID-19, obesity is an important and growing public health concern. Using a mouse model of high fat diet-induced obesity, a team of scientists at the University of California, Riverside, has found that, compared to males, female mice are protected against obesity and inflammation because they secrete more of an immune protein called RELMalpha. "Our study identifies immune cells and RELMalpha in causing these sex-specific differences in the immune response to obesity," said Meera G. Nair, an associate professor of biomedical sciences in the School of Medicine, who co-led the study published in eLife with Djurdjica Coss, a professor of biomedical sciences. RELM, or resistin-like molecules, constitute a family of proteins secreted by mammals that are highly expressed in infectious and inflammatory diseases. One of these proteins, RELMalpha, is quickly triggered in the mouse body following infection and serves to protect the body's tissues. It has a sequence and function similar to resistin in humans. "RELMalpha regulates two immune cell types: the anti-inflammatory macrophage and the eosinophil," Nair said. Macrophages and eosinophils are types of disease-fighting white blood cells but can be damaging to the body in the absence of infection. "In contrast, males expressed less RELMalpha, had less eosinophils, and had inflammatory macrophages that promoted obesity." When the researchers deleted RELMalpha in female mice, they found the mice were no longer protected from obesity, had fewer eosinophils, and had inflammatory macrophages -- similar to male mice. "However, we were able to reduce obesity in these female mice by treating them with eosinophils or with RELMalpha, suggesting promising therapeutic targets," Nair said. "We are the first to map this pathway in females that protects against obesity." The research team found RELMalpha deficiency had significant effects in males also, but to a lesser extent than females. "In our experiments, female mice had higher levels of RELMalpha than males, which likely explains why RELMalpha deficiency affected females more than males," Coss said. "The implications of our study are that consideration of sex differences is critical to tackle metabolic diseases such as obesity." According to Nair, the study is novel in showing a previously unrecognized role for RELMalpha in modulating metabolic and inflammatory responses during diet-induced obesity that is sex dependent. "Our results highlight a critical 'RELMalpha-eosinophil-macrophage axis' that functions in females to protect from diet-induced obesity and inflammation," she said. "Promoting these pathways could, therefore, provide novel therapies for combating obesity." Nair and Coss were joined in the study by Jiang Li, Rebecca E Ruggiero-Ruff, Yuxin He, Xinru Qiu, Nancy Lainez, Pedro Villa, and Adam Godzik of UCR. The study was supported by grants to Nair and Coss from the National Institutes of Health.