Mucosal Immunology最新文献_第4页

Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases. 诱导型而非构成型胰腺REG/ REG异构体受肠道微生物群和胰腺疾病的调节。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-19 DOI: 10.1016/j.mucimm.2025.05.003

Yixuan D Zhou, Macy R Komnick, Fabiola Sepulveda, Grace Liu, Elida Nieves-Ortiz, Kelsey Meador, Ornella Ndatabaye, Aliia Fatkhullina, Asha Bozicevich, Braden Juengel, Natalie J Wu-Woods, Paulina M Naydenkov, Johnathan Kent, Nathaniel Christiansen, Maria Lucia Madariaga, Piotr Witkowski, Rustem F Ismagilov, Daria Esterházy

{"title":"Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases.","authors":"Yixuan D Zhou, Macy R Komnick, Fabiola Sepulveda, Grace Liu, Elida Nieves-Ortiz, Kelsey Meador, Ornella Ndatabaye, Aliia Fatkhullina, Asha Bozicevich, Braden Juengel, Natalie J Wu-Woods, Paulina M Naydenkov, Johnathan Kent, Nathaniel Christiansen, Maria Lucia Madariaga, Piotr Witkowski, Rustem F Ismagilov, Daria Esterházy","doi":"10.1016/j.mucimm.2025.05.003","DOIUrl":"10.1016/j.mucimm.2025.05.003","url":null,"abstract":"The REG/Reg gene locus encodes a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether REG/Reg family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in humans and mice, the pancreas and gut differed in REG/Reg isoform levels and preferences, with the duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select Reg members in gut and pancreas. These Reg members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as \"inducible\" and others as \"constitutive\". Indeed, in pancreatic ductal adenocarcinoma and pancreatitis models, only inducible Reg members were upregulated in the pancreas. While intestinal Reg expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of REG/Reg isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated Reg response.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Notch-activated basophils support intestinal CD4⁺ T cell fate and function during Trichuris muris infection. 缺口激活的嗜碱性粒细胞支持寄生虫感染期间肠道CD4+ T细胞的命运和功能。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-16 DOI: 10.1016/j.mucimm.2025.05.004

Lauren M Webb, Lindsey M Warner, Eric Y Helm, Bridget M Mooney, Pavithra Sundaravaradan, Macy K Matheson, Tighe Christopher, Alejandra Lopez Espinoza, Elia D Tait Wojno

{"title":"Notch-activated basophils support intestinal CD4+ T cell fate and function during Trichuris muris infection.","authors":"Lauren M Webb, Lindsey M Warner, Eric Y Helm, Bridget M Mooney, Pavithra Sundaravaradan, Macy K Matheson, Tighe Christopher, Alejandra Lopez Espinoza, Elia D Tait Wojno","doi":"10.1016/j.mucimm.2025.05.004","DOIUrl":"10.1016/j.mucimm.2025.05.004","url":null,"abstract":"Helminth infections affect billions of people worldwide and cause substantial morbidity. Intestinal helminth infection provokes Type 2 inflammation orchestrated by CD4+ T helper type 2 (Th2) cells. Th2 cells cooperate with group 2 innate lymphoid cells (ILC2s) to produce interleukin (IL)-4 and IL-13 that prompt an epithelial \"weep and sweep\" response to drive parasite clearance. Tissue-specific cues optimize CD4+ T cell responses, but the mechanisms regulating intestinal Th2 responses remain unclear. Previously, we identified that the Notch signaling pathway in basophils, rare granulocytes, drove effective parasite clearance and an optimal Th2 response during Trichuris muris infection, a mouse model of human whipworm infection. Here we report that basophil-intrinsic Notch was required for infection-elicited Th2 cytokine responses and a broader IL-4 production program across intestinal CD4+ T cell subsets. In vitro, basophils supported CD4+ T cell IL-4 production in a contact-dependent manner, independent of basophil-secreted factors and MHC class II, but dependent on autocrine IL-4 production from CD4+ T cells. In vivo, basophil-intrinsic Notch mediated basophil-Th2 cell interactions in the cecum during infection. Thus, Notch-programmed basophils act in a contact-dependent manner to optimize intestinal CD4+ T cell function during helminth infection. These findings improve our understanding of the tissue-specific mechanisms regulating intestinal CD4+ T cell responses at inflamed mucosal barriers during Type 2 immunity.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parasite and host immune factors that impact the development of a mucosal vaccine for Cryptosporidium. 影响隐孢子虫粘膜疫苗研制的寄生虫和宿主免疫因素。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-14 DOI: 10.1016/j.mucimm.2025.05.002

Maria Merolle, Boris Striepen, Christopher A Hunter

引用次数: 0

Improved humanized mouse model of Staphylococcus aureus infection. 改进的金黄色葡萄球菌感染人源化小鼠模型。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-10 DOI: 10.1016/j.mucimm.2025.05.001

Hui Wang, Dane Parker

{"title":"Improved humanized mouse model of Staphylococcus aureus infection.","authors":"Hui Wang, Dane Parker","doi":"10.1016/j.mucimm.2025.05.001","DOIUrl":"10.1016/j.mucimm.2025.05.001","url":null,"abstract":"Staphylococcus aureus is a significant cause of pulmonary infections, but existing mouse models fail to recapitulate human-specific responses. In this study, we developed a novel mouse model of S. aureus infection using humanized mice implanted with autologous fetal lung tissue. We show that these human lung implants support S. aureus survival and dissemination. Immunological profiling revealed extensive immune cell death after infection and an absence of chemokine induction. Transcriptomic profiling of the human lung implants revealed significant changes in gene expression, including NF-κB and JAK/STAT signaling. We identified upregulation of Cyp24a1, suggesting a role for vitamin D metabolism in host defense, but it had a mild effect on dissemination. Examination of the bacterial response to the host environment, found downregulation of virulence factors and metabolic genes, and upregulation of stress response pathways. The importance of the heat shock response in bacterial survival was shown as hrcA-deficient S. aureus exhibited reduced tissue colonization. These findings underscore the utility of this humanized lung model for studying S. aureus pathogenesis and bacterial adaptation to the human pulmonary environment.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diet-induced dyslipidemia enhances IFN-γ production in mycolic acid-specific T cells and affects mycobacterial control. 饮食诱导的血脂异常增强了霉菌酸特异性T细胞中IFN-γ的产生并影响分枝杆菌的控制。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-03 DOI: 10.1016/j.mucimm.2025.04.009

Yen-Lin Lin, Chyung-Ru Wang

{"title":"Diet-induced dyslipidemia enhances IFN-γ production in mycolic acid-specific T cells and affects mycobacterial control.","authors":"Yen-Lin Lin, Chyung-Ru Wang","doi":"10.1016/j.mucimm.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.009","url":null,"abstract":"Dyslipidemia, characterized by altered lipid profiles, influences host immune responses against infections, including Mycobacterium tuberculosis (Mtb). While the effects of dyslipidemia on conventional T cell responses are well documented, its impact on group 1-CD1 restricted T cells, a distinct subset of lipid antigen-specific unconventional T cells, during Mtb infection remains unclear. In this study, we developed a double-transgenic mouse model expressing human group 1 CD1 (hCD1Tg) and mycolic acid (MA)-specific CD1b-restricted T cell receptor (DN1Tg) in a Rag-deficient and low-density lipoprotein receptor-deficient background to investigate how diet-induced dyslipidemia affects the functionality of MA-specific T cells and their role in anti-Mtb immunity. We found that diet-induced dyslipidemia led to increased IFN-γ production by MA-specific T cells, which promoted mycobacterial clearance in vitro. Mechanistically, this enhanced IFN-γ production was associated with increased TCR signaling and enhanced glycolysis in DN1 T cells, rather than changes in antigen presentation by dendritic cells. However, dyslipidemia also increased apoptosis in DN1 T cells, which may have impaired their ability to control mycobacterial infection in vivo, resulting in reduced bacterial clearance. These findings highlight a complex interplay between diet-induced dyslipidemia and lipid antigen-specific T-cell responses in Mtb infection, providing insights for potential therapeutic strategies to mitigate dyslipidemia-induced changes in T-cell functions.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-ST2 antibody reduces airway hyperresponsiveness mediated by monocyte-derived macrophages during influenza A infection. 抗st2抗体降低甲型流感感染期间由单核细胞来源的巨噬细胞介导的气道高反应性。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-05-02 DOI: 10.1016/j.mucimm.2025.04.008

Rohin Chakraborty, Julia Chronopoulos, Rui Sun, Arina Morozan, Sydney Joy, Maziar Divangahi, Anne-Marie Lauzon, James G Martin

{"title":"Anti-ST2 antibody reduces airway hyperresponsiveness mediated by monocyte-derived macrophages during influenza A infection.","authors":"Rohin Chakraborty, Julia Chronopoulos, Rui Sun, Arina Morozan, Sydney Joy, Maziar Divangahi, Anne-Marie Lauzon, James G Martin","doi":"10.1016/j.mucimm.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.008","url":null,"abstract":"Influenza A virus (IAV) infections trigger asthma attacks and cause airway hyperresponsiveness (AHR) in murine models. However, the mechanism by which AHR is induced remains to be fully elucidated. Here, we show that targeting the interleukin (IL)-33 suppression of tumorigenicity 2 (ST2) receptor complex with an anti-ST2 antibody during acute IAV infection of C57BL/6 mice reduced AHR, without affecting expansion of ILC2s and independently of IL-13. Among the lung inflammatory cells, the anti-ST2 antibody selectively reduced the monocyte-derived macrophages (MMs). Furthermore, AHR was reduced in C-C chemokine receptor 2 (CCR2)-knockout mice that have deficient MM recruitment. Depletion of MMs achieved by anti-Ly6C antibody administration also reduced AHR. The treatment of airway smooth muscle (ASM) with conditioned medium from IL-33-treated human THP-1-derived macrophages enhanced potassium chloride-induced ASM contraction. These findings suggest that MMs contribute to acute AHR following IAV infection in an IL-33-dependent manner, but independent of the ILC2/IL-13 axis. Additionally, IL-33 stimulates the release of macrophage-derived mediators that enhance airway smooth muscle contraction, offering a potential mechanistic basis for IAV-induced AHR.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial single-cell analysis identifies placental villi structuraland immune remodeling across gestation. 空间单细胞分析鉴定胎盘绒毛结构和整个妊娠期的免疫重塑。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-04-25 DOI: 10.1016/j.mucimm.2025.04.005

Suganthinie Velagala, Long Phan, Chino Eke, Analie Fernandes, Tyler A Rice, Oluwabunmi Olaloye, Liza Konnikova

{"title":"Spatial single-cell analysis identifies placental villi structuraland immune remodeling across gestation.","authors":"Suganthinie Velagala, Long Phan, Chino Eke, Analie Fernandes, Tyler A Rice, Oluwabunmi Olaloye, Liza Konnikova","doi":"10.1016/j.mucimm.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.005","url":null,"abstract":"Pregnancies rely upon the balance between fetal and maternal immune systems. Employing imaging mass cytometry, this study creates a spatial map landscape to unravel the cellular dynamics within the placental villi (PV). Consistent with previous data we report structural remodeling in PV, highlighted by increased syncytial trophoblasts, vascular smooth muscle cells, and endothelial cells in term PV. Additionally, we identified that rare immune populations including dendritic cells, innate lymphoid cells, and myeloid-derived suppressor cells in mid-gestation were more abundant and activated than in term placentas, suggesting a potentially tolerogenic state. Conversely, various macrophage subtypes were increased and in combination with rare T-cells exhibited heightened activation markers, possibly indicating increased signaling in preparation for parturition. In mid-gestation, fibroblasts had increased interactions with trophoblasts, while term samples exhibited close adjacencies between trophoblasts, vascular smooth muscle cells, and macrophages. This study offers insights into the PV cellular composition changes between mid and full-term samples, providing a foundation for future studies to understand the mechanisms of preterm birth and other pregnancy complications.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RSV infection in neonatal mice and gastrointestinal microbiome alteration contribute to allergic predisposition. 新生小鼠的RSV感染和胃肠道微生物组改变有助于过敏易感性。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-04-23 DOI: 10.1016/j.mucimm.2025.04.007

Alexander D Ethridge, Kazuma Yagi, Llilian Arzola Martínez, Andrew J Rasky, Susan B Morris, Nicole R Falkowski, Gary B Huffnagle, Nicholas W Lukacs

{"title":"RSV infection in neonatal mice and gastrointestinal microbiome alteration contribute to allergic predisposition.","authors":"Alexander D Ethridge, Kazuma Yagi, Llilian Arzola Martínez, Andrew J Rasky, Susan B Morris, Nicole R Falkowski, Gary B Huffnagle, Nicholas W Lukacs","doi":"10.1016/j.mucimm.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.007","url":null,"abstract":"Severe respiratory syncytial virus (RSV) infection during infancy is associated with a 2 to 4-fold increased risk for the development of wheezing and asthma. Recent studies have implicated microbiome changes, either within the lung or gut, during early life can also affect the development of pulmonary disease. Our studies demonstrate long-term gastrointestinal and lung microbiome changes following early life (EL) RSV infection. To determine the respective roles of ELRSV infection and the gut microbiome, we performed germ-free neonatal infection and microbiome colonization using a microbiome from an uninfected animal followed by cockroach allergen (CRA)-induced asthma 4 weeks later. Germ-free animals with ELRSV infection displayed increased airway disease that was diminished by microbiome colonization, including airway hyperreactivity (AHR), mucus, and eosinophil infiltration. To address the role of virus induced gastrointestinal microbiome alterations, we utilized GF mice conventionalized with RSV-associated or naive microbiomes followed by CRA-induced disease. Transfer of neonatal microbiome taken during acute RSV infection did not alter the allergic response to CRA. However, the transfer of a naive adult microbiome conferred protection from enhanced AHR in response to CRA whereas an RSV associated microbiome did not. Taken together, our data indicate that microbiome alteration and early life RSV infection both contribute to allergic predisposition.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PAD4 inhibition impacts immune responses in SARS-CoV-2 infection. 抑制PAD4对SARS-CoV-2感染免疫应答的影响

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-04-19 DOI: 10.1016/j.mucimm.2025.04.006

Caio Santos Bonilha, Flavio Protasio Veras, Anderson Dos Santos Ramos, Giovanni Freitas Gomes, Robertha Mariana Rodrigues Lemes, Eurico Arruda, José Carlos Alves-Filho, Thiago Mattar Cunha, Fernando Queiroz Cunha

{"title":"PAD4 inhibition impacts immune responses in SARS-CoV-2 infection.","authors":"Caio Santos Bonilha, Flavio Protasio Veras, Anderson Dos Santos Ramos, Giovanni Freitas Gomes, Robertha Mariana Rodrigues Lemes, Eurico Arruda, José Carlos Alves-Filho, Thiago Mattar Cunha, Fernando Queiroz Cunha","doi":"10.1016/j.mucimm.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.006","url":null,"abstract":"Protein arginine deiminase 4 (PAD4) has emerged as a potential therapeutic target for various diseases due to its role in promoting neutrophil extracellular trap (NET) formation. NETs, composed of DNA and antimicrobial proteins, serve as a defense mechanism against pathogens but can also drive lung injury, particularly in SARS-CoV-2 infection. In this study, we examined the effects of PAD4 inhibition on clinical outcomes and adaptive immunity within the context of SARS-CoV-2 infection. Our results show that PAD4 pharmacological inhibition reduced lung NET concentration and improved clinical outcomes, similar to treatment with recombinant human DNase (rhDNase), which degrades NET structure. However, in contrast to rhDNase, PAD4 targeting diminished virus-specific T cell responses by impairing dendritic cell antigen presentation and reducing IL-2 signaling by affecting its production by T cells. In line with these observations, PAD4 pharmacological inhibition diminished antigen-specific T cell responses in a model of lung inflammation. These findings highlight the importance of carefully evaluating PAD4 as a therapeutic target in COVID-19, given its potential to compromise adaptive immune responses crucial for fighting the virus.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A zebrafish model of intestinal epithelial damage reveals macrophages and igfbp1a as major modulators of mucosal healing. 斑马鱼肠上皮损伤模型显示巨噬细胞和igfbp1a是粘膜愈合的主要调节剂。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-04-17 DOI: 10.1016/j.mucimm.2025.04.004

Rodrigo A Morales Castro, Bianca C Kern, Angélica Díaz-Basabe, Eveline R Meinen, Danxia Zhao, Yuqing Zhou, Francisca Castillo, Gustavo Monasterio, Vlad Farcas, Myra N Chávez, Jennifer Fransson, Eduardo J Villablanca

{"title":"A zebrafish model of intestinal epithelial damage reveals macrophages and igfbp1a as major modulators of mucosal healing.","authors":"Rodrigo A Morales Castro, Bianca C Kern, Angélica Díaz-Basabe, Eveline R Meinen, Danxia Zhao, Yuqing Zhou, Francisca Castillo, Gustavo Monasterio, Vlad Farcas, Myra N Chávez, Jennifer Fransson, Eduardo J Villablanca","doi":"10.1016/j.mucimm.2025.04.004","DOIUrl":"10.1016/j.mucimm.2025.04.004","url":null,"abstract":"Promoting intestinal regeneration and enhancing mucosal healing have emerged as promising therapeutic alternatives for treating intestinal disorders that compromise epithelial barrier integrity and function. However, the cellular and molecular mechanisms underlying these processes remain poorly understood. This knowledge gap is partly due to the lack of reliable and cost-effective in vivo models for studying the mechanisms governing intestinal damage and regeneration. Here, we developed a controlled, inducible, and targeted intestinal epithelial cell (IEC) ablation transgenic zebrafish model that recapitulates features of intestinal damage and regeneration observed in humans. Single-cell RNAseq and live imaging revealed accumulation of macrophages in the recovering intestine, contributing to its regeneration. Furthermore, we observed overexpression of insulin-like growth factor binding protein 1a (igfbp1a) during intestinal damage. Morpholino-mediated knockdown of igfbp1a exacerbated intestinal damage and impaired subsequent regeneration. In summary, we introduced a novel zebrafish model of intestinal damage that enables in vivo high-throughput screening for identifying and validating novel modulators of mucosal healing and intestinal regeneration.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0