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Antigen-inexperienced memory-phenotype CD8 + T cells are categorized as innate memory cells in the thymus or virtual memory (VM) CD8 + T cells in peripheral tissues. The key distinction between these cell types is their differing responses to IL-4, but the minimal effect of IL-4 on VM CD8 + T cell expansion in the periphery is not well understood. To address this, we investigated the development of VM CD8 + T cells in the periphery of IL-4 knockout (KO) C57BL/6 mouse. CD8 + splenocytes were isolated from the spleen of wilt-type (WT) and IL-4 KO mice, followed by single-cell RNA sequencing and Seurat analysis on sorted CD8 + cells using the 10x Genomics platform. This study identified various CD8 + T cell subtypes, including naïve, effector, IFN-stimulated, true memory (TM), and VM T cells. VM CD8 + T cells were characterized by high expression of Cd44, Cxcr3, Il2rb, Eomes, Tbx21, Ly6c2, and low expression of Itga4. In IL-4-deficient mouse, macrophages were significantly reduced, while memory T cell populations showed a slight increase compared to WT mouse. Both Itga4 + TM and Itga4 - VM CD8 + T cells were more abundant in IL-4 KO mouse. Within the VM T cell group, Ly6a - VM CD8 + T cells were reduced, while Ly6a  +  VM CD8 + T cells were increased relative to WT mouse. These Ly6a + VM CD8 + cells exhibited high expression of genes linked to type I IFN signaling, such as Isg15, Ifit1, and Stat1. Our findings suggest that IFN-influenced Ly6a  +  VM CD8 + T cells play a role in maintaining the peripheral VM CD8 + T cell population in the absence of IL-4., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The prevalence of metabolic syndrome (MetS), a cluster of serious medical conditions that raise the risk of lung cancer, has increased worldwide. Tobacco smoking (TS) potentially increases the risk of developing MetS. Despite the potential association of MetS with lung cancer, preclinical models that mimic human diseases, including TS-induced MetS, are limited. Here we evaluated the impact of exposure to tobacco smoke condensate (TSC) and two representative tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNK) and benzo[a]pyrene (BaP), on MetS development in mice., Materials and Methods: FVB/N or C57BL/6 mice were exposed to vehicle, TSC, or NNK and BaP (NB) twice weekly for 5 months. The serum levels of total cholesterol (TCHO), triglycerides, high-density lipoprotein (HDL), blood glucose, and metabolites, along with glucose tolerance and body weight, were measured., Key Findings: Compared with those of vehicle-treated mice, mice with TSC or NB exposure displayed major phenotypes associated with MetS, including increased serum levels of TCHO, triglycerides, and fasting and basal blood glucose and decreased glucose tolerance, and serum levels of HDL. These MetS-associated changes were found in both FVB/N and C57BL/6 mice that were susceptible or resistant to carcinogen-induced tumorigenesis, respectively, indicating that tumor formation is not involved in the TSC- or NB-mediated MetS. Moreover, oleic acid and palmitoleic acid, which are known to be associated with MetS, were significantly upregulated in the serum of TSC- or NB-treated mice compared with those in vehicle-treated mice., Significance: Both TSC and NB caused detrimental health problems, leading to the development of MetS in experimental mice., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)