DSpace Community: KAIST Dept. of Biological SciencesKAIST Dept. of Biological Scienceshttp://hdl.handle.net/10203/5262024-03-15T09:45:24Z2024-03-15T09:45:24ZThe crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areataShin, Jung-MinKim, Kyung MinChoi, Mi SooPark, SanghyunHong, DongkyunJung, Kyung-EunSeo, Young-JoonKim, Chang DeokYang, HanseulLee, Younghttp://hdl.handle.net/10203/3169732023-12-28T05:00:12Z2024-01-01T00:00:00ZTitle: The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata
Authors: Shin, Jung-Min; Kim, Kyung Min; Choi, Mi Soo; Park, Sanghyun; Hong, Dongkyun; Jung, Kyung-Eun; Seo, Young-Joon; Kim, Chang Deok; Yang, Hanseul; Lee, Young
Abstract: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFN? and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFN? and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFN? and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.2024-01-01T00:00:00ZGinsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor CoregulatorsKim, KyuraeKim, Myung-HoKang, Ji InBaek, Jong-InJeon, Byeong-MinKim, Ho MinKim, Sun ChangJeong, Won-Ilhttp://hdl.handle.net/10203/3176192024-01-10T05:01:06Z2024-01-01T00:00:00ZTitle: Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators
Authors: Kim, Kyurae; Kim, Myung-Ho; Kang, Ji In; Baek, Jong-In; Jeon, Byeong-Min; Kim, Ho Min; Kim, Sun Chang; Jeong, Won-Il
Abstract: Background: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). Methods: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRα−/− mice. Results: Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRα−/− mice. Conclusion: GF2 alters the binding affinities of LXRα coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD.2024-01-01T00:00:00ZThe transcription factor NFIL3/E4BP4 regulates the developmental stage–specific acquisition of basophil functionPark, JiyeonCho, YuriYang, DongchanYang, HanseulLee, DaeyoupKubo, MasatoKang, Suk-Johttp://hdl.handle.net/10203/3179152024-01-26T07:00:36Z2024-01-01T00:00:00ZTitle: The transcription factor NFIL3/E4BP4 regulates the developmental stage–specific acquisition of basophil function
Authors: Park, Jiyeon; Cho, Yuri; Yang, Dongchan; Yang, Hanseul; Lee, Daeyoup; Kubo, Masato; Kang, Suk-Jo
Abstract: Background
Basophils are rare but important effector cells in many allergic disorders. Contrary to their early progenitors, the terminal developmental processes of basophils in which they gain their unique functional properties are unknown.
Objective
We sought to identify a novel late-stage basophil precursor and a transcription factor regulating the terminal maturation of basophils.
Methods
Using flow cytometry, transcriptome analysis, and functional assays, we investigated the identification and functionality of the basophil precursors as well as basophil development. We generated mice with basophil-specific deletion of nuclear factor IL-3 (NFIL3)/E4BP4 and analyzed the functional impairment of NFIL3/E4BP4-deficient basophils in vitro and in vivo using an oxazolone-induced murine model of allergic dermatitis.
Results
We report a new mitotic transitional basophil precursor population (referred to as transitional basophils) that expresses the FcεRIα chain at higher levels than mature basophils. Transitional basophils are less responsive to IgE-linked degranulation but produce more cytokines in response to IL-3, IL-33, or IgE cross-linking than mature basophils. In particular, we found that the expression of NFIL3/E4BP4 gradually rises as cells mature from the basophil progenitor stage. Basophil-specific deletion of NFIL3/E4BP4 reduces the expression of genes necessary for basophil function and impairs IgE receptor signaling, cytokine secretion, and degranulation in the context of murine atopic dermatitis.
Conclusions
We discovered transitional basophils, a novel late-stage mitotic basophil precursor cell population that exists between basophil progenitors and postmitotic mature basophils. We demonstrated that NFIL3/E4BP4 augments the IgE-mediated functions of basophils, pointing to a potential therapeutic regulator for allergic diseases.2024-01-01T00:00:00ZAssessment Methods for Problematic Eating Behaviors in Children and Adolescents With Autism Spectrum DisorderLee M.Lee S.Sohn J.-W.Kim K.W.Choi H.J.http://hdl.handle.net/10203/3183442024-03-01T02:00:12Z2024-01-01T00:00:00ZTitle: Assessment Methods for Problematic Eating Behaviors in Children and Adolescents With Autism Spectrum Disorder
Authors: Lee M.; Lee S.; Sohn J.-W.; Kim K.W.; Choi H.J.
Abstract: Autism spectrum disorder (ASD) can be associated with eating problems. However, currently, there is a lack of established guidelines for assessing and addressing eating behaviors in individuals with ASD. This gap in research exists due to the challenges associated with using traditional assessment methods, which may lead to discrepancies in responses and unintentional potential biases from caregivers. In this review, we provided a comprehensive overview of various eating behaviors commonly observed in individuals with ASD. These behaviors include 1) food neophobia, 2) selective eating, 3) binge eating, 4) food avoidance, 5) chewing and swallowing problems, 6) pica, 7) rumination, 8) rituals, and 9) problematic behaviors. Furthermore, we provide a perspective of utilizing digital tools: 1) augmentative and alternative communication; 2) ecological momentary assessment; and 3) video analysis, behavioral analysis, and facial expression analysis. This review explores existing assessment methods and suggests novel assessment aiding together.2024-01-01T00:00:00Z