Mucosal Immunology最新文献

Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling. 微生物群通过激活TCR和IL-15信号通路促进CD39在γδ上皮内淋巴细胞中的表达。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-07-17 DOI: 10.1016/j.mucimm.2025.07.005

Sara Alonso, Harsimran Kaur, Luo Jia, Mai-Uyen Nguyen, Alyssa Laguerta, Andrew Fong, Neema Skariah, Rafael J Argüello, Michael P Verzi, Mahima Swamy, Ken S Lau, Karen L Edelblum

{"title":"Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling.","authors":"Sara Alonso, Harsimran Kaur, Luo Jia, Mai-Uyen Nguyen, Alyssa Laguerta, Andrew Fong, Neema Skariah, Rafael J Argüello, Michael P Verzi, Mahima Swamy, Ken S Lau, Karen L Edelblum","doi":"10.1016/j.mucimm.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.07.005","url":null,"abstract":"Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide continuous surveillance of the intestinal epithelium. We report that mice harboring a microbiota-specific hyperproliferative γδ IEL (γδHYP) phenotype also upregulate the expression of the ectonucleotidase CD39, a marker of regulatory γδ T cells. Enhanced TCR and IL-15 signaling correlates with a progression from a naïve-like CD39neg γδ IEL to a more mature, tissue-adapted CD39hi IEL population. We found that TCR γδ activation drives CD122-mediated CD39 upregulation on γδHYP IELs and increased mucosal IL-15 further amplifies CD39 expression in these cells. Further investigation revealed that CD39 induction requires sustained exposure to the γδHYP-associated microbiota. Moreover, CD39hi γδ IELs exhibit a reduced capacity to produce pro-inflammatory cytokine, which may explain the lack of histopathology in γδHYP mice. Overall, our study identifies a previously unappreciated mechanism by which an altered microbiota amplifies CD39 expression on γδHYP IELs, leading to the expansion of γδ IELs with regulatory potential.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668044","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

TRIM33 prevents the exacerbation of allergic asthma by restricting the overactivation of alveolar macrophages. TRIM33通过限制肺泡巨噬细胞的过度活化来防止过敏性哮喘的加重。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-07-16 DOI: 10.1016/j.mucimm.2025.07.003

Jiaoyan Lv, Ziyan Su, Tao Wu, Yujie Tian, Xin Liu, Jiachen Liu, Xiaoguang Li, Wenlong Lai, Chen Dong, Li Wu

{"title":"TRIM33 prevents the exacerbation of allergic asthma by restricting the overactivation of alveolar macrophages.","authors":"Jiaoyan Lv, Ziyan Su, Tao Wu, Yujie Tian, Xin Liu, Jiachen Liu, Xiaoguang Li, Wenlong Lai, Chen Dong, Li Wu","doi":"10.1016/j.mucimm.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.07.003","url":null,"abstract":"Alveolar macrophages (AMs) and dendritic cells (DCs) are the two major types of primary innate immune cells in allergic asthma and their functions were elaborately regulated during the progression of asthma. Tripartite motif-containing protein 33 (TRIM33) is a multifunctional protein that regulates differentiation and function of immune cells. However, its role in AMs and DCs in the context of allergic asthma remained unclear. Herein, we found that specific deletion of TRIM33 in AM and DCs (ItgaxCre-GFPTrim33fl/fl mice) affected their homeostasis in lung and induced aggravated allergic asthma. Though reduced in number, TRIM33 deficient CD11b± DCs exhibited comparable potency in triggering allergic asthma. Replacing Trim33-/- AMs with normal AMs could alleviate the aggravated HDM-induced airway inflammation and Th2 responses in ItgaxCre-GFPTrim33fl/fl mice. Moreover, Trim33-/- AMs exhibited stronger activation status and became an additional cellular source of CCL2 when encountered the allergen, thereby promoting the recruitment of CD11b+ DCs into lung and draining lymph nodes where they amplifying Th2 responses in ItgaxCre-GFPTrim33fl/fl mice. Our study revealed a crucial role of TRIM33 in controlling the aggravation of allergic asthma via repressing AM overactivation.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668045","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

Type-I interferons in Vulvovaginal Candidiasis: Mechanism of epithelial early defense and immune regulation against Candida albicans. i型干扰素在外阴阴道念珠菌病中的作用：上皮早期防御机制和对白色念珠菌的免疫调节。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-07-10 DOI: 10.1016/j.mucimm.2025.07.001

Emilse Rodriguez, Constanza Savid-Frontera, Sofía C Angiolini, María Luisa Hernáez Sánchez, María Soledad Miró, María Estefanía Viano, Paula A Icely, Cinthia C Stempin, María Cecilia Rodriguez-Galán, Concha Gil, Claudia E Sotomayor

{"title":"Type-I interferons in Vulvovaginal Candidiasis: Mechanism of epithelial early defense and immune regulation against Candida albicans.","authors":"Emilse Rodriguez, Constanza Savid-Frontera, Sofía C Angiolini, María Luisa Hernáez Sánchez, María Soledad Miró, María Estefanía Viano, Paula A Icely, Cinthia C Stempin, María Cecilia Rodriguez-Galán, Concha Gil, Claudia E Sotomayor","doi":"10.1016/j.mucimm.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.07.001","url":null,"abstract":"Vulvovaginal candidiasis (VVC) is a mucosal infection predominantly caused by Candida albicans, affecting over three-quarters of immunocompetent women worldwide. While the female genital tract mucosa is the primary defense against the fungus, the specific immune mechanisms involved in this host-pathogen interaction remain largely unknown. In this study, we explored the relevance of type-I interferons (IFNs-I) pathway using both in vitro and in vivo models of VVC. Our quantitative proteomic analysis revealed that C. albicans induces the activation of the IFNs-I pathway in human epithelial cells (ECs) of the female genital tract shortly after exposure to the fungus. Additionally, we identified β-glucans as a crucial fungal component involved in triggering this pathway. Using a VVC model in IFN-α/β receptor-deficient (Ifnar1-/-) mice, we demonstrated that IFNs-I regulate the fungal burden, C. albicans epithelial invasion, polymorphonuclear neutrophils (PMNs) recruitment, inflammatory tissue response, local cytokine balance, and the composition of T cell subsets in the draining lymph nodes. These findings underscore the pivotal role of the IFNs-I pathway in ECs-mediated responses against C. albicans, especially in the early stages of VVC development, offering insights into potential therapeutic targets for this condition.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619091","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

Tofacitinib ameliorates Campylobacter-induced intestinal pathology by suppressing IFNγ producing ILCs and T cells. 托法替尼通过抑制IFNγ产生的ilc和T细胞改善弯曲杆菌诱导的肠道病理。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-07-03 DOI: 10.1016/j.mucimm.2025.06.010

Anna A Korchagina, Sergey A Shein, Wayne T Muraoka, Justin Nguyen, Qiangxing Chen, Anna A Tumanova, Austin W Todd, Carlos E Rivera, Rita Tamayo, Paolo Casali, Ekaterina Koroleva, Alexei V Tumanov

{"title":"Tofacitinib ameliorates Campylobacter-induced intestinal pathology by suppressing IFNγ producing ILCs and T cells.","authors":"Anna A Korchagina, Sergey A Shein, Wayne T Muraoka, Justin Nguyen, Qiangxing Chen, Anna A Tumanova, Austin W Todd, Carlos E Rivera, Rita Tamayo, Paolo Casali, Ekaterina Koroleva, Alexei V Tumanov","doi":"10.1016/j.mucimm.2025.06.010","DOIUrl":"10.1016/j.mucimm.2025.06.010","url":null,"abstract":"Patients with autoimmune diseases are more susceptible to foodborne infections, which can be exacerbated by immunosuppressive therapy. Tofacitinib, a JAK/STAT pathway inhibitor, was recently approved for the treatment of ulcerative colitis, yet its effects on the pathogenesis of intestinal infections remain unclear. Here, we examined the impact of oral tofacitinib treatment in a mouse model of Campylobacter jejuni (C. jejuni) infection. Our results show that early tofacitinib administration attenuates intestinal pathology without affecting bacterial colonization. Specifically, tofacitinib suppressed CXCL1, CXCL2, CCL2 chemokine expression by intestinal epithelial cells, limiting recruitment of monocytes and neutrophils to the gut. In addition, JAK/STAT inhibition reduced IFNγ-producing innate lymphoid cells (ILCs) and T cells in the gut. Furthermore, tofacitinib suppressed IFNγ production and ameliorated intestinal disease in humanized mice. Cell-fate mapping revealed that tofacitinib predominantly inhibited IFNγ production by NK1.1- ILCs derived from NKp46- progenitors and reduced NK1.1- ILC proliferation without affecting ILC3 to ILC1 plasticity. Notably, tofacitinib ameliorated intestinal disease even in the absence of T cells. These findings suggest that tofacitinib alleviates C. jejuni-induced colitis by reducing proinflammatory cytokine production by monocytes/macrophages/epithelial cells and suppressing IFNγ secretion by ILCs and T cells, while preserving antibacterial defenses.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564969","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

Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection. 成纤维细胞衍生的CSF1维持肠道粘膜巨噬细胞的定植以抵抗细菌感染。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-07-01 DOI: 10.1016/j.mucimm.2025.06.011

Daichi Nonaka, Soichiro Yoshida, Kenta Nakano, Xiaojun Li, Tadashi Okamura, Eiji Umemoto, Taisho Yamada, Miyuki Watanabe, Shozo Jinno, Minako Ito, Makoto Tsuda, Naoto Noguchi, Jean X Jiang, Eriko Sumiya, Shinichiro Sawa

{"title":"Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection.","authors":"Daichi Nonaka, Soichiro Yoshida, Kenta Nakano, Xiaojun Li, Tadashi Okamura, Eiji Umemoto, Taisho Yamada, Miyuki Watanabe, Shozo Jinno, Minako Ito, Makoto Tsuda, Naoto Noguchi, Jean X Jiang, Eriko Sumiya, Shinichiro Sawa","doi":"10.1016/j.mucimm.2025.06.011","DOIUrl":"10.1016/j.mucimm.2025.06.011","url":null,"abstract":"Macrophages play essential roles in immune defense and tissue homeostasis, but the mechanisms underlying their colonization in the gut mucosa remain incompletely understood. Here, we identify CSF1, primarily derived from fibroblasts, as the dominant factor maintaining mucosal macrophage colonization, whereas IL-34 deficiency alone has a minimal impact. We reveal that CSF1R ligands originate from distinct cellular sources: macrophages at the upper villus region depend on fibroblast-derived CSF1 and IL-34, while macrophages in the lower villus and the submucosal (lower villus + SM) region are regulated by CSF1 from both fibroblasts and endothelial cells. Additionally, within the lower villus + SM region, CSF1-producing CD81+ LepR+ fibroblasts directly interact with CD163+ macrophages, forming a localized niche. The loss of CSF1 in fibroblasts results in accelerated systemic dissemination of Salmonella Typhimurium, highlighting fibroblast-derived CSF1 as a key regulator of gut macrophage function in host defense. Collectively, our findings uncover a previously unrecognized fibroblast-macrophage crosstalk that governs gut macrophage homeostasis and immunity.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560556","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 novel link driving immune cell-fibroblast interactions in intestinal fibrosis. 肠道纤维化中驱动免疫细胞-成纤维细胞相互作用的新联系。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-06-27 DOI: 10.1016/j.mucimm.2025.06.009

Gaurav Chauhan, Ido Veisman, Florian Rieder

引用次数: 0

Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation. 单细胞RNA谱鉴定糖尿病相关粘膜炎症中免疫细胞群的变化。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-06-27 DOI: 10.1016/j.mucimm.2025.06.008

Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves

{"title":"Single-cell RNA profiling identifies immune cell population shifts in diabetes associated mucosal inflammation.","authors":"Bushra Alghamdi, Min Liu, Xin Huang, Rahul Debnath, Hamideh Afzali, Michael Troka, Akira Hasuike, Quinn Easter, Mi Zhou, Kevin Byrd, Michael Gonzalez, Kang I Ko, Dana T Graves","doi":"10.1016/j.mucimm.2025.06.008","DOIUrl":"10.1016/j.mucimm.2025.06.008","url":null,"abstract":"Poorly controlled diabetes significantly worsens periodontal disease, affecting millions worldwide, yet the mechanisms driving this destructive synergy remain unclear. We generated single-cell RNA sequencing profiles of diabetic periodontal tissue, revealing increased γδ T-cells, a loss of Tregs and greater neutrophil polarization as key mediators of diabetes-enhanced periodontitis. Flow cytometry confirmed significant expansion of IL-17A+ γδ+ T-cells and reduced Tregs in diabetic mice, with parallel findings of elevated CD3+IL-17A+ cells and reduced Tregs in human diabetic periodontal specimens. scRNAseq determined that diabetes caused a global increase in pro-inflammatory and a decrease in pro-resolving transcripts and enhanced inflammatory neutrophil polarization. Selective γδ T-cell inhibition reversed diabetes-enhanced periodontal destruction while minimally affecting normoglycemic controls and returned neutrophil infiltration to normoglycemic levels. These findings point to unique aspects of diabetes-induced dysregulation, and implicate γδ T-cells as a driving factor and point to them as a potential therapeutic target in periodontitis and other diabetic complications.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528986","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

Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice. 外源性ephrin-A3逆转孕激素处理小鼠阴道上皮屏障保护的丧失。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-06-24 DOI: 10.1016/j.mucimm.2025.06.007

Mohan Liu, Rodolfo D Vicetti Miguel, Kristen Aceves, Thomas L Cherpes

{"title":"Exogenous ephrin-A3 reverses loss of vaginal epithelial barrier protection in progestin-treated mice.","authors":"Mohan Liu, Rodolfo D Vicetti Miguel, Kristen Aceves, Thomas L Cherpes","doi":"10.1016/j.mucimm.2025.06.007","DOIUrl":"10.1016/j.mucimm.2025.06.007","url":null,"abstract":"Desmosomes are junctional complexes that confer mechanical strength and enhance barrier protection at mucosal epithelial surfaces by anchoring intermediate filaments to plasma membrane. These roles are best defined in cutaneous epithelium, but we previously identified lower levels of the desmosomal cadherins desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and loss of barrier function in vaginal epithelium of mice treated systemically with the progestin depot medroxyprogesterone acetate (DMPA). We also showed these changes were avoided in mice treated with both DMPA and a conjugated equine estrogen vaginal cream. We extend these earlier results in the current investigation, identifying ephrin-A3 (EFNA3) as an important regulator of desmosomal cadherin gene expression in murine vaginal epithelial tissue. Moreover, topical treatment of mice with recombinant EFNA3 (rEFNA3) significantly increased vaginal expression of DSG1 and partially reversed the loss of vaginal epithelial barrier function induced by DMPA treatment. Consistent with this improvement in vaginal epithelial barrier protection, mortality caused by genital herpes simplex virus type 2 infection was delayed, but not prevented, in mice administered DMPA and rEFNA3 vs. DMPA alone. Together, current studies identify EFNA3 as a key regulator of desmosomal structure and function in vaginal epithelium and newly suggest that ephrin-Eph signaling pathways will provide an important target for enhancing vaginal epithelial integrity and barrier function.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506861","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

Memory T cell formation and phenotype varies across intestinal compartments. 记忆T细胞的形成和表型在不同的肠室中是不同的。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-06-16 DOI: 10.1016/j.mucimm.2025.06.005

Sarah Sandford, Maximilien Evrard, Thomas N Burn, Susan N Christo, Marina H Yakou, Andreas Obers, Yannick O Alexandre, Laura K Mackay, Scott N Mueller

{"title":"Memory T cell formation and phenotype varies across intestinal compartments.","authors":"Sarah Sandford, Maximilien Evrard, Thomas N Burn, Susan N Christo, Marina H Yakou, Andreas Obers, Yannick O Alexandre, Laura K Mackay, Scott N Mueller","doi":"10.1016/j.mucimm.2025.06.005","DOIUrl":"10.1016/j.mucimm.2025.06.005","url":null,"abstract":"Numerous studies have shown that tissue-resident memory T (TRM) cells form in the intestine following pathogen clearance. However, most knowledge of intestinal TRM cells has derived from analyses restricted to the small intestine (SI). In contrast, less is known about TRM cell formation in the large intestine (LI). Here, we compared the abundance and phenotype of memory T cells across intestinal compartments. Using mouse models of infection, we observed that fewer memory T cells formed in the LI compared to the SI. Moreover, we found that T cells in the epithelium and lamina propria of the LI colon and caecum were phenotypically distinct from SI counterparts, comprising Ly6C-expressing CD8+ TRM cells with a distinct cytokine and granzyme profile. Using both loss- and gain-of-function approaches, we identified site-specific TGF-β dependencies, whereby Ly6C+CD103- TRM cells developed independently of TGF-β in both the SI and LI. In contrast, augmenting TGF-β signalling preferentially expanded Ly6C-TRMpopulations in the LI but not the SI, indicating that TGF-β signalling drives TRMcell heterogeneity between these compartments. Together, these findings underscore how regional differences in TRM cell responsiveness to local cues shape their development, phenotype, and function along the gastrointestinal tract.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294133","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

Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids. 胎盘炎症驱动的T细胞记忆形成通过内源性糖皮质激素促进后代的过敏反应。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2025-06-13 DOI: 10.1016/j.mucimm.2025.06.006

Myoung Seung Kwon, Won Hyung Park, Jeongwoo La, Chae Won Kim, Heung Kyu Lee

{"title":"Placental inflammation-driven T cell memory formation promotes allergic responses in offspring via endogenous glucocorticoids.","authors":"Myoung Seung Kwon, Won Hyung Park, Jeongwoo La, Chae Won Kim, Heung Kyu Lee","doi":"10.1016/j.mucimm.2025.06.006","DOIUrl":"10.1016/j.mucimm.2025.06.006","url":null,"abstract":"Maternal exposure to environmental change during pregnancy is a critical determinant of offspring health and disease. Previous epidemiological studies have reported that maternal inflammation is linked to an increased incidence of postnatal allergy in offspring, although the underlying mechanisms remain largely unexplored. In this study, we employed a lipopolysaccharide-induced maternal inflammation murine model and found that offspring from dams with maternal immune activation (MIA) exhibited heightened allergic responses to house dust mite allergen. MIA offspring showed an increase in CD4+ T cell responses, which were mediated by increased T cell survival after activation, leading to promoting central and resident memory T cells formation. During maternal inflammation, TNF-α was identified as a crucial cytokine driving the heightened allergic response in offspring. TNF-α activates placental neutrophil, leading to placental necrosis. In parallel with placental damage, MIA offspring demonstrated increased glucocorticoid secretion in response to stress. Blockade of the glucocorticoid pathway during the sensitization phase mitigated the enhanced T cell memory response in MIA offspring, highlighting a mechanism by which maternal inflammation potentially modulates immune responses in offspring. Our findings elucidate one of the pathways by which maternal inflammation can influence postnatal immune regulation in offspring.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302558","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