Sung Won Lee

1. Natural killer T (NKT) and NKT-like cells are heterogeneous innate-like T cells that express natural killer (NK) cell receptors (NKRs) and bridge innate and adaptive immunity by rapidly releasin...

While chronic alcohol consumption is an established risk factor for lipid metabolic dysregulation, the underlying genetic mediators remain largely elusive. This study investigated the synergistic impact of CCDC63 (coiled-coil domain containing 63) polymorphisms and alcohol intake on dyslipidemia risk within a Korean cohort. Leveraging data from the KARE study (N = 6655; 4327 dyslipidemia cases vs. 2328 controls), we analyzed SNPs across the CCDC63 locus via Affymetrix SNP Array 5.0. Logistic regression, adjusted for age and sex, was performed to evaluate genotype–phenotype association and gene–environment interactions induced by alcohol exposure duration. Three intronic variants (rs10849915, rs11065756, and rs2238149) were significantly associated with dyslipidemia (OR ≥ 1.15, p < 0.005). Notably, stratified analysis revealed a clear gene–environment interaction. In ever-drinkers, the G-allele of rs10849915 was significantly associated with a higher risk of dyslipidemia (OR = 1.23, p < 0.05), significantly lower γ-GTP levels (β = −8.08), and reduced HDL (β = −1.42). However, no such genetic associations were observed in the non-drinking group (p > 0.05 for all traits). Our findings demonstrate that CCDC63 variants specifically modulate lipid metabolism and hepatic enzyme levels in an alcohol-dependent manner. The paradoxical association—lower γ-GTP yet higher dyslipidemia risk in drinkers—suggests that CCDC63 plays a critical role in the complex interplay between alcohol exposure and systemic lipid homeostasis.

While chronic alcohol consumption is an established risk factor for lipid metabolic dysregulation, the underlying genetic mediators remain largely elusive. This study investigated the synergistic impact of CCDC63 (Coiled-Coil Domain Containing 63) polymorphisms and alcohol intake on dyslipidemia risk within a Korean cohort. Leveraging data from the KARE study (n=6,655; 4,327 dyslipidemia cases vs. 2,328 controls), we analyzed SNPs across the CCDC63 locus via Affymetrix SNP Array 5.0. Logistic regression, adjusted for age and sex, was performed to evaluate genotype-phenotype association, and gene-environment interactions by alcohol exposure duration. Three intronic variants (rs10849915, rs11065756, and rs2238149) were significantly associated with dyslipidemia (OR ≥1.15, P CCDC63 variants specifically modulate lipid metabolism and hepatic enzyme levels in an alcohol-dependent manner. The paradoxical association—lower γ-GTP yet higher dyslipidemia risk in drinkers—suggests that CCDC63 plays a critical role in the complex interplay between alcohol exposure and systemic lipid homeostasis.

The SWItch3-related gene (SRG3) is a core component of ATP-dependent SWI/SNF complexes, which are crucial for regulating immune cell development and function (e.g., macrophages and CD4⁺ T cells), embryonic development, and non-immune cell differentiation. Notably, SRG3 overexpression has been shown to polarize macrophages in the central nervous system toward an anti-inflammatory M2 phenotype, thereby protecting against the development of experimental autoimmune encephalomyelitis in mice. However, the effect of SRG3 on immune responses in adipose tissues remains unclear. To address this issue, we examined the cellularity and inflammatory status of adipose tissue in B10.PL mice overexpressing the SRG3 gene under the ubiquitous β-actin promoter (SRG3^β-actin). Interestingly, SRG3 overexpression significantly reduced adipocyte size in both white and brown adipose tissues, without affecting the overall adipose tissue weight. Such phenotypic effects might be associated with the improved glucose tolerance observed in SRG3^β-actin B10.PL mice. Moreover, we found that SRG3 overexpression down-regulates IL1β-expressing M1 macrophages, leading to a significant decrease in the M1/M2 macrophage ratio. Additionally, SRG3^β-actin B10.PL mice showed a dramatic reduction in neutrophils as well as IL1β- and IL17-producing T cells in adipose tissues. Taken together, our results indicate that SRG3 plays a vital role in maintaining immune homeostasis within adipose tissues.

Graphene oxide (GO), a carbon-based material with oxygen-containing functional groups, can be applied in biomedicine for drug delivery, cancer therapy, and tissue regeneration. We have previously shown that nanoscale-sized graphene oxide (NGO), an oxidized graphene derivative, exhibits effective anti-inflammatory activity in a murine model of sepsis mediated by T helper (Th)1-promoting cytokines such as IFNγ and TNFα. However, whether NGO influences Th2-induced skin inflammation remains unclear. To address this issue, we employed an ovalbumin (OVA) plus aluminum hydroxide (Alum)-induced Th2-mediated skin inflammation model in conjunction with OVA-specific DO11.10 T cell receptor transgenic Balb/c mice. In vivo NGO injection upon OVA/Alum sensitization down-regulated OVA-elicited antigen-specific Th2 cells and GATA3-expressing Th2-type regulatory T cells. Next, we examined the effect of NGO injection on OVA/Alum-induced atopic dermatitis (AD)-like skin inflammation. NGO-injected mice exhibited significantly decreased Th2 disease phenotypes (e.g., a lower clinical score, decreased epidermal thickness and Th2 cell differentiation, and fewer infiltrated mast cells and basophils in skin lesions) compared with vehicle-injected control mice. Overall, our results suggest that NGOs are promising therapeutic materials for treating allergic diseases such as AD.

Yoon-Joo SONG, Sung Won LEE, Hyun-Seok JIN, Sangwook PARK. Korean J Clin Lab Sci. 2024;56:66-72. https://doi.org/10.15324/kjcls.2024.56.1.66

Beta-glucan (β-glucan) is a natural polysaccharide produced by fungi, bacteria, and plants. Although it has been reported that β-glucan enhances innate immune memory responses, it is unclear whether different types of β-glucans display similar immune effects. To address this issue, we employed zymosan (β-1,3-glycosidic linkage) and pustulan (β-1,6-glycosidic linkage) to investigate their in vivo effects on innate memory immune responses. We examined the changes of innate memory-related markers in macrophages and natural killer (NK) cells, two immune cell types that display innate memory characteristics, at two different time points (16 h and 7 days) after β-glucan stimulation. We found that short-term (16 h) zymosan treatment significantly induced macrophages to upregulate IL15 production and increased surface IL15Rα expression on NK cells. In addition, long-term (7 days) zymosan treatment significantly induced macrophages to upregulate the expression of innate memory-related markers (e.g., TNFα, HIF1α, and mTOR) and induced NK cells to express enhanced levels of KLRG1, known as an innate memory-like marker. Our results provide support that zymosan can be an effective adjuvant to promote innate memory immune responses, providing a bridge between innate and adaptive immune cells to enhance various immune responses such as those directed against tumors.

Interleukin-7 (IL-7) plays a vital role in the homeostasis of CD4⁺ and CD8⁺ T cells. Although IL-7 has been implicated in T helper (Th)1- and Th17-mediated autoinflammatory diseases, its role in Th2-type allergic disorders, such as atopic dermatitis (AD), remains unclear. Thus, to elucidate the effects of IL-7 deficiency on AD development, we generated IL-7-deficient AD-prone mice by backcrossing IL-7 knockout (KO) B6 mice onto the NC/Nga (NC) mouse strain, a model for human AD. As expected, IL-7 KO NC mice displayed defective development of conventional CD4⁺ and CD8⁺ T cells compared with wild type (WT) NC mice. However, IL-7 KO NC mice presented with enhanced AD clinical scores, IgE hyperproduction, and increased epidermal thickness compared with WT NC mice. Moreover, IL-7 deficiency decreased Th1, Th17, and IFN-γ-producing CD8⁺ T cells but increased Th2 cells in the spleen of NC mice, indicating that a reduced Th1/Th2 ratio correlates with severity of AD pathogenesis. Furthermore, significantly more basophils and mast cells infiltrated the skin lesions of IL-7 KO NC mice. Taken together, our findings suggest that IL-7 could be a useful therapeutic target for treating Th2-mediated skin inflammations, such as AD.

Although 3-aminopropyl functionalized magnesium phyllosilicate nanoparticles (hereafter aminoclay nanoparticles, ACNs) are well-known nanomaterials employed as drug carriers, their effects on immune cells remain unclear. To address this issue, we explored murine dendritic cells (DCs) as these cells belong to the innate arm of the immune system and function as antigen-presenting cells to elicit adaptive immune responses. We examined the in vitro effects of ACNs on DCs isolated from B6 mice. ACN treatment significantly down-regulated the expression of inflammasome-related markers, including NLRP3, caspase-1, and IL1β. The ACNs-induced anti-inflammatory DC phenotype was further confirmed by down-regulation of the AKT/mTOR/HIF1α signaling pathway. Such anti-inflammatory effects of ACNs on DCs occurred independently of DC subtypes. To document the effects of ACNs on DCs more clearly, we examined their anti-inflammatory effects on lipopolysaccharide (LPS)-activated DCs. As expected, excessive inflammatory responses (increased mitochondrial ROS and Th1-type cytokines such as IL12 and IL1β) of LPS-activated DCs were dramatically attenuated by ACN treatment. Furthermore, ACNs down-regulated IFNγ production by antigen-specific CD4⁺ T cells, which is consistent with a reduced inflammatory phenotype of DCs. Overall, our results provide support for employing ACNs as drug delivery materials with therapeutic potential to control inflammatory disorders.