Shin Ae Kang

Obesity, an escalating global health crisis, is characterized by adipose tissue hypertrophy and chronic low-grade inflammation. Although anti-obesity drugs can induce weight loss, their use is limited by adverse effects, underscoring the need for safer therapeutic strategies. In this study, we generated a recombinant form of Trichinella spiralis-derived macrophage migration inhibitory factor (rTs-MIF) and investigated its anti-inflammatory and anti-obesity effects via immunometabolic regulation. Male C57BL/6 mice fed a 45% high-fat diet were orally administered rTs-MIF, and its effects were evaluated by measuring fat mass, glucose metabolism, serum cytokines, liver histology, and adipose tissue parameters. In 3T3-L1 cells, we examined the effects of rTs-MIF on adipocyte differentiation, obesity-related gene expression, and intracellular signaling pathways. Oral rTs-MIF suppressed body weight gain, reduced fat mass, improved glucose levels, and decreased the food efficiency ratio. It also lowered pro-inflammatory cytokines and increased markers associated with M2 macrophages. In 3T3-L1 cells, rTs-MIF inhibited adipocyte differentiation and reduced the expression of lipogenic transcription factors and mouse Mif while modulating AKT and p44/42 MAPK signaling. These findings identify rTs-MIF as a potential bioactive candidate that ameliorates obesity by regulating the immune–metabolic axis.

Balamuthia mandrillaris is a causative agent of granulomatous amebic encephalitis, a rare but often fatal condition. To investigate the role of T helper (Th) cell subsets in the immune response against B. mandrillaris, we examined 3 mouse strains with distinct immunological profiles: C57BL/6 (Th1-dominant), BALB/c (Th2-dominant), and ICR (balanced Th1/Th2). Mice were infected intranasally with 1×105 amoebae. Body weight and neurologic symtoms were monitored weekly, and cytokine expression was assessed biweekly over 6 weeks. Minimal weight loss and no mortality were observed in C57BL/6 mice, whereas BALB/c and ICR mice exhibited significant early and delayed mortality, respectively. Interleukin-17A expression was notably elevated in C57BL/6 mice compared with the other strains. These findings indicate that a robust Th17 response, particularly interleukin-17A production, is a critical component of the host defense against B. mandrillaris infection.

The ovalbumin (OVA)-alum mouse model, which induces a Th2-biased immune response, is commonly used to study allergic airway inflammation. However, the artificial nature of this model limits its relevance to environmental or infection-related airway diseases. The free-living environmental protozoan Acanthamoeba is a potential trigger of airway inflammation, but its immune mechanisms remain largely unknown. To compare these 2 models of airway inflammation, this study carried out microarray-based transcriptomic analysis of lung tissue obtained from mice with OVA-alum treatment or intranasal Acanthamoeba exposure. Compared to controls, OVA-alum treatment induced broad transcriptional changes involving >2,900 probes (fold change ≥1.5); Acanthamoeba exposure led to a substantially weaker response, with <500 probes affected at the same threshold. Unlike the OVA-alum–treated group, the Acanthamoeba-exposed mice showed minimal overlap with only 5 genes significantly downregulated, suggesting a distinct immune activation profile. Downregulation of genes related to the immunoglobulin variable region (Ighv1-58 and Igkv3-10) and eosinophil function (Rnase2a) in the Acanthamoeba group suggest suppression of a typical Th2/humoral response. Heatmap and clustering analysis demonstrated clear separation between the Acanthamoeba, OVA-alum, and control groups. Taken together, these results suggest that Acanthamoeba induces a unique airway immune response that is markedly different from traditional Th2-dominant inflammation, and may be a more suitable model for studying environmentally-induced or infection-related respiratory diseases.

Although adipose stem cell (ASC)-derived extracellular vesicles (EVs) are as effective as ASCs in the suppression of Th2 cell-mediated eosinophilic inflammation, the role of identified pulmonary genes has not been well documented. Thus, we assessed the immunomodulatory effects of paraoxonase-1 (PON1) on allergic airway inflammation in a mouse model of asthma. Five-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of PON1 on allergic airway inflammation, the intranasal and intraperitoneal injections of recombinant mouse serum PON1 (5 μg/50 μL) were performed before the OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, and eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), cytokine profiles of BALF and lung draining lymph nodes (LLNs), the expression of interleukin (IL)-25 and transforming growth factor (TGF)-β in mouse lung epithelial cell (MLE-12 cell), and dendritic cell (DC) differentiation. The intraperitoneal and intranasal administration of PON1 significantly decreased AHR, total inflammatory cells and eosinophils in BALF, eosinophilic airway inflammation, serum total, and OVA-specific IgE. PON1 treatment, which marked reduced IL-4, IL-5, and IL-13 in the BALF and LLN but significantly increased interferon-γ and TGF-β. Furthermore, PON1 treatment significantly decreased the expression of IL-25 and increased TGF-β in MLE-12 cells. The expressions of CD40, CD80, and CD86 in immature DCs were significantly increased by PON1 treatment. The administration of PON1 ameliorated allergic airway inflammation and improved AHR through the downregulation of IL-4, IL-5, and IL-13 and upregulation of TGF-β in asthmatic mice. Furthermore, PON1 treatment decreased Th2-mediated inflammation induced by Aspergillus protease antigen by decreasing IL-25 and increasing TGF-β.

Although mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have evaluated the immunomodulatory capacity of MSC-derived EVs in patients with asthma. Thus, we assessed the effects of adipose stem cell (ASC)-derived EVs on cytokine expression and regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. PBMCs (1 × 10⁶ cells/mL) were isolated from asthmatic patient and healthy controls and co-cultured with 1 μg/mL of ASC-derived EVs. Th (T helper) 1-, Th2-, and Treg-related cytokine expression, fluorescence-activated cell sorting analysis of CD4⁺CD25⁺FOXP3⁺ T cells, and co-stimulatory molecules were analyzed before and after ASC-derived EV treatment. The expression levels of IL-4 and costimulatory molecules such as CD83 and CD86 were significantly higher in PBMCs of asthmatic patients than in control PBMCs. However, ASC-derived EV treatment significantly decreased the levels of interleukin (IL)-4 and co-stimulatory molecules such as CD83 and CD86 in the phytohemagglutinin (PHA)-stimulated PBMC of asthmatic patients. Furthermore, ASC-derived EVs remarkably increased the transforming growth factor-β (TGF-β) levels and expression of Tregs in the PBMC of asthmatic patients. ASC-derived EVs induce Treg expansion and have immunomodulatory effects by downregulating IL-4 and upregulating TGF-β in PBMCs of asthmatic patients.

Although helminth parasites have different life cycles, their hosts share similar immune responses involving Th2 cell-type. Here, we extracted proteins from the larvae of Anisakis simplex complex and Trichinella spiralis to identify common and specific antigens (or allergens) associated with the Th2 immune response. We performed two-dimensional electrophoresis analysis and Matrix-assisted laser desorption ionization–time of flight/time of flight (MALDI-TOF/TOF) experiments. We found 13 potentially immunogenic proteins, which included 5 spots specific to T. spiralis and 8 common to T. spiralis and A. simplex, by tandem mass spectrometry. These molecules were identified structurally as actin, tropomyosin, col cuticle N domain-containing protein, and heat shock proteins. We also identified molecules related to parasite-host immune modulation and interactions. Our results may contribute to reveal potential roles of immunological proteins in parasite-derived immune modulation.

The nanosized vesicles secreted from various cell types into the surrounding extracellular space are called extracellular vesicles (EVs). Although mesenchymal stem cell-derived EVs are known to have immunomodulatory effects in asthmatic mice, the role of identified pulmonary genes in the suppression of allergic airway inflammation remains to be elucidated. Moreover, the major genes responsible for immune regulation in allergic airway diseases have not been well documented. This study aims to evaluate the immunomodulatory effects of secretoglobin family 1C member 1 (SCGB1C1) on asthmatic mouse models. C57BL/6 mice were sensitized to ovalbumin (OVA) using intraperitoneal injection and were intranasally challenged with OVA. To evaluate the effect of SCGB1C1 on allergic airway inflammation, 5 μg/50 μL of SCGB1C1 was administrated intranasally before an OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), the cytokine profiles of BALF and lung-draining lymph nodes (LLN), and the T cell populations in LLNs. The intranasal administration of SCGB1C1 significantly inhibited AHR, the presence of eosinophils in BALF, eosinophilic inflammation, goblet cell hyperplasia in the lung, and serum total and allergen-specific IgE. SCGB1C1 treatment significantly decreased the expression of interleukin (IL)-5 in the BALF and IL-4 in the LLN, but significantly increased the expression of IL-10 and transforming growth factor (TGF)-β in the BALF. Furthermore, SCGB1C1 treatment notably increased the populations of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in asthmatic mice. The intranasal administration of SCGB1C1 provides a significant reduction in allergic airway inflammation and improvement of lung function through the induction of Treg expansion. Therefore, SCGB1C1 may be the major regulator responsible for suppressing allergic airway inflammation.

Benzimidazole derivatives can effectively treat nematode parasitic infections; however, some derivatives demand distinct administrative strategies depending on plasma concentration and patient conditions. Numerous studies have examined the potential of natural extracts to exert parasiticidal activity with minimal side effects. Herein, we examined the potential parasiticidal effects of Torreya nucifera extract. The pericarps of T. nucifera were extracted with methanol, dried, and the pellet was dissolved in hot water (Tn-Phw). We designed four individual mouse experiments to clarify the prophylactic and therapeutic effects of Tn-Phw on Trichinella spiralis infection. Also, 100 L1 larvae were isolated and treated with Tn-Phw (10 mg/mL) in vitro to confirm the killing effect. Furthermore, we microscopically examined the morphology of L1 larvae to confirm the parasite-killing effect and analyzed the morphology using a scanning electron microscope (SEM). The expression of three molting-related genes was confirmed to determine whether Tn-Phw induced morphological changes in L1 larvae. Following treatment with Tn-Phw, L1 larvae death was observed after 16 h. Following SEM examination, the healthy muscle larvae showed striated ridges and wrinkles; this was not observed in extract-treated muscle larvae. Expression levels of the three molting-related genes did not differ between the Tn-Phw-treated and control groups. T. spiralis-infected mice pretreated with Tn-Phw showed significantly reduced muscle larva infection when compared with control mice. In all experiments, treatment with Tn-Phw afforded preventive and therapeutic effects against T. spiralis infection and parasitism. Natural substances against nematode parasites could be developed as therapeutic agents with few side effects and enhanced parasiticidal efficacy.

The chemokine receptor CCR7 is a well‐established homing receptor for dendritic cells (DCs) and T‐cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7‐induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis‐infected mice. The CCR7‐expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7‐expressing cells in PLNs increased by more than 30% at 28 days post‐infection; however, this increase was significantly inhibited in CCR7‐blocked mice treated with CCR7‐specific antibodies. T helper 2 (Th2)‐and regulatory T (T_reg)‐related cytokine levels were also reduced by CCR7‐specific antibody treatment. CCR7‐blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis‐specific IgE in the serum were observed in CCR7‐blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection‐induced suppression of Th2‐ and T_reg‐related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and T_reg cell responses.

Background: Previous studies have shown that Echinococcus granulosus cystic fluid can alleviate Th2 allergic airway inflammatory responses by increasing the number of CD4⁺CD25⁺ Foxp3⁺T (regulatory T; Treg) cells. Parasite‐derived extracellular vesicles (EV) are known to not only promote parasite infection by communicating between parasites but also regulate the inflammatory response by acting as an immunomodulatory agent in the host.Methods: To evaluate the effect of EV extracted from the cystic fluid of E. granulosus on allergic airway inflammation, gene expression was investigated after administering EV to mouse lung epithelial cells (MLE‐12) following 2 h of pretreatment with Aspergillus proteins. An allergic airway inflammation animal model was used to investigate the regulation of the inflammatory response by EV and induced with ovalbumin.Results: EV treatment significantly reduced airway resistance and the number of eosinophils and other immune cells in the bronchoalveolar lavage fluid and Th2‐ and Th17‐related cytokine levels. EV pretreatment decreased the number of IL‐4⁺CD4⁺T cells and increased the number of Treg cells in the lung‐draining lymph nodes and spleen.Conclusions: Echinococcus granulosus cystic fluid derived EV ameliorated Th2 allergic airway inflammatory through Treg cells, similar to whole cystic fluid treatment. Thus, EV may be important immunomodulatory molecules in cystic fluid.