Mucosal Immunology最新文献_第10页

Lung influenza virus-specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells 肺部流感病毒特异性记忆 CD4 T 细胞的位置和最佳细胞因子的产生取决于与肺部抗原呈递细胞的相互作用。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.001

{"title":"Lung influenza virus-specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells","authors":"","doi":"10.1016/j.mucimm.2024.06.001","DOIUrl":"10.1016/j.mucimm.2024.06.001","url":null,"abstract":"<div><div>Influenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterizing changes to the lung landscape and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and major histocompatibility complex (MHC)II+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found in lung airways but reduced interferon-γ expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of programmed death ligand 1 (PD1) than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-low counterparts. This distinction in location was lost in mice treated with anti-MHCII antibodies. These data suggest that sustained antigen presentation in the lung impacts the formation of memory CD4 T cells by regulating their cytokine production and location.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 843-857"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of the SST-SSTR5 signaling pathway enhances corneal wound healing in diabetic mice 激活 SST-SSTR5 信号通路可促进糖尿病小鼠角膜伤口愈合

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.002

{"title":"Activation of the SST-SSTR5 signaling pathway enhances corneal wound healing in diabetic mice","authors":"","doi":"10.1016/j.mucimm.2024.06.002","DOIUrl":"10.1016/j.mucimm.2024.06.002","url":null,"abstract":"<div><div>Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice. In addition, we discovered that topical administration of exogenous SST significantly improved re-epithelialization and nerve regeneration following diabetic corneal epithelial abrasion. Further analysis showed that topical SST significantly reduced the expression of injury inflammation-related genes, inhibited neutrophil infiltration, and shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 in diabetic corneas' healing. Moreover, the application of L-817,818, an agonist of the SST receptor type 5 subtype, significantly reduced the inflammatory response following epithelial injury and markedly improved the process of re-epithelialization and nerve regeneration in mice. Taken together, these data suggest that activation of the SST-SST receptor type 5 pathway significantly ameliorates diabetes-induced abnormalities in corneal wound repair in mice. Targeting this pathway may provide a novel strategy to restore impaired corneal wound closure and nerve regeneration in diabetic patients.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 858-870"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways by CD101 CD101 对代谢、免疫调节和抗微生物途径的细胞特异性调节。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.004

{"title":"Cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways by CD101","authors":"","doi":"10.1016/j.mucimm.2024.06.004","DOIUrl":"10.1016/j.mucimm.2024.06.004","url":null,"abstract":"<div><div>T lymphocytes and myeloid cells express the immunoglobulin-like glycoprotein cluster of differentiation (CD)101, notably in the gut. Here, we investigated the cell-specific functions of CD101 during dextran sulfate sodium (DSS)-induced colitis and <em>Salmonella enterica</em> Typhimurium infection. Similar to conventional CD101<sup>−/−</sup> mice, animals with a regulatory T cell-specific <em>Cd101</em> deletion developed more severe intestinal pathology than littermate controls in both models. While the accumulation of T helper 1 cytokines in a CD101-deficient environment entertained DSS-induced colitis, it impeded the replication of <em>Salmonella</em> as revealed by studying CD101<sup>−/−</sup> x interferon-g<sup>−/−</sup> mice. Moreover, CD101-expressing neutrophils were capable to restrain <em>Salmonella</em> infection <em>in vitro</em> and <em>in vivo</em>. Both cell-intrinsic and -extrinsic mechanisms of CD101 contributed to the control of bacterial growth and spreading. The CD101-dependent containment of <em>Salmonella</em> infection required the expression of <em>Irg-1</em> and <em>Nox2</em> and the production of itaconate and reactive oxygen species. The level of intestinal microbial antigens in the sera of inflammatory bowel disease patients correlated inversely with the expression of CD101 on myeloid cells, which is in line with the suppression of CD101 seen in mice following DSS application or <em>Salmonella</em> infection. Thus, depending on the experimental or clinical setting, CD101 helps to limit inflammatory insults or bacterial infections due to cell type-specific modulation of metabolic, immune-regulatory, and anti-microbial pathways.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 892-910"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn’s disease in a retinoic acid–deficient manner 人类肠道基质细胞以缺乏维甲酸的方式促进正常粘膜的稳态，但在克罗恩病中则促进炎症。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.009

{"title":"Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn’s disease in a retinoic acid–deficient manner","authors":"","doi":"10.1016/j.mucimm.2024.06.009","DOIUrl":"10.1016/j.mucimm.2024.06.009","url":null,"abstract":"<div><div>Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentin<sup>+</sup>CD90<sup>+</sup>smooth muscle actin<sup>−</sup> SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn’s disease SCs (Crohn’s SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs). We also show that microbe-stimulated Crohn’s SCs, which are more inflammatory than stimulated normal SCs, induced less RA-regulated differentiation of mucosal dendritic cells (DCs) (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory interferon-γ<sup>hi</sup>/interleukin-17<sup>hi</sup> T cells than normal SCs. Explaining these results, Crohn’s SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal and, thus, synthesized less RA than normal SCs. These findings uncover a microbe–SC–DC crosstalk in which luminal microbes induce Crohn’s disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 958-972"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impaired neutrophil migration underpins host susceptibility to infectious colitis 中性粒细胞迁移障碍是宿主易患传染性结肠炎的基础。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.008

{"title":"Impaired neutrophil migration underpins host susceptibility to infectious colitis","authors":"","doi":"10.1016/j.mucimm.2024.06.008","DOIUrl":"10.1016/j.mucimm.2024.06.008","url":null,"abstract":"<div><div><em>Citrobacter rodentium</em> models infection with enteropathogenic <em>Escherichia coli</em> and ulcerative colitis (UC). While C57BL/6 (C57) mice recover, C3H/HeN (C3H) mice succumb to infection, partially due to increased colonic neutrophil elastase activity, also seen in UC patients; however, the underlying cause was unknown. Here, we found that bone marrow, blood, and colonic C57 neutrophils expressed (CD)11b<sup>Hi</sup> and reached the infected colonic lumen, where they underwent productive NETosis. In contrast, while the number of C3H neutrophils increased in the bone marrow, blood, and colon, they remained CD11b<sup>Lo</sup> and got trapped in the submucosa, away from <em>C. rodentium</em>, where they underwent harmful NETosis. CD11b<sup>Lo</sup> neutrophils in C3H mice infected with CR<sub>i9</sub>, which triggers expression of neutrophil chemoattractants, reached the colonization site, resulting in host survival. UC patient neutrophils also displayed decreased levels of the activation/differentiation markers CD16/CXCR4. These results, suggesting that neutrophil malfunction contributes to exacerbated colitis, provide insight for future therapeutic prospects.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 939-957"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis Git2 缺乏可通过 NF-κB-CXCL1/CXCL12 途径促进肠道中 MDSCs 的招募，并改善坏死性小肠结肠炎。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.07.006

Huijuan Le , Yanyan Wang , Jiefei Zhou , Dan Li , Zizhen Gong , Fangxinxing Zhu , Jian Wang , Chunyan Tian , Wei Cai , Jin Wu

{"title":"Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis","authors":"Huijuan Le , Yanyan Wang , Jiefei Zhou , Dan Li , Zizhen Gong , Fangxinxing Zhu , Jian Wang , Chunyan Tian , Wei Cai , Jin Wu","doi":"10.1016/j.mucimm.2024.07.006","DOIUrl":"10.1016/j.mucimm.2024.07.006","url":null,"abstract":"<div><div>Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches. GIT2 (G-protein-coupled receptor kinase interacting proteins 2) can affect innate and adaptive immunity and has been involved in multiple inflammatory disorders. In this study, we investigated whether GIT2 participates in the pathogenesis of NEC. Here we found that intestinal <em>Git2</em> gene expression was significantly increased in NEC patients and NEC mice, which positively correlated with the tissue damage severity, and <em>Git2</em> deficiency could potently protect against NEC development in mice. Mechanistically, <em>Git2</em> gene knockout dramatically increased the recruitment of MDSCs in the intestine, and <em>in vivo</em> depletion of MDSCs almost completely abrogated the protective effect of <em>Git2</em> deficiency on NEC. Moreover, <em>Git2</em> deficiency induced MDSCs intestinal accumulation mainly relied on CXCL1/CXCL12 signaling, as evidenced by the significant increment of CXCL1 and CXCL12 levels in intestinal epithelium of <em>Git2</em><sup>-/-</sup> mice and dramatically decrease of MDSCs accumulation in intestine as well as increase of NEC severity upon treatment of CXCL1/CXCL12 pathway inhibitors. In addition, <em>Git2</em> deficiency induced up-regulation of CXCL1 and CXCL12 is at least partially mediated through activating NF-κB signaling. Thus, our findings suggest that GIT2 is involved in the pathogenesis of NEC, and targeting GIT2 may be a potential preventive and therapeutic approach for NEC.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1060-1071"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis 代谢活跃的嗜中性粒细胞是结核分枝杆菌的容许生态位。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.05.007

{"title":"Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis","authors":"","doi":"10.1016/j.mucimm.2024.05.007","DOIUrl":"10.1016/j.mucimm.2024.05.007","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that interferon-γ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 825-842"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atopic dermatitis and food allergy: More than sensitization 特应性皮炎与食物过敏：不仅仅是过敏。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.005

引用次数: 0

Regulatory T cells restrict immunity and pathology in distal tissue sites following a localized infection 调节性 T 细胞限制了局部感染后远端组织部位的免疫和病理变化。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.007

{"title":"Regulatory T cells restrict immunity and pathology in distal tissue sites following a localized infection","authors":"","doi":"10.1016/j.mucimm.2024.06.007","DOIUrl":"10.1016/j.mucimm.2024.06.007","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are well-known to mediate peripheral tolerance at homeostasis, and there is a growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated the role of Tregs in immunity and disease in various tissue compartments in the context of “mild” vaginal Zika virus infection. We found that Tregs are critical to generating robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg-sufficient mice, in which there is no CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 923-938"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammation of the nasal mucosa is associated with susceptibility to experimental pneumococcal challenge in older adults 鼻黏膜炎症与老年人对实验性肺炎球菌挑战的易感性有关。

IF 7.9 2区医学

Mucosal Immunology Pub Date : 2024-10-01 DOI: 10.1016/j.mucimm.2024.06.010

{"title":"Inflammation of the nasal mucosa is associated with susceptibility to experimental pneumococcal challenge in older adults","authors":"","doi":"10.1016/j.mucimm.2024.06.010","DOIUrl":"10.1016/j.mucimm.2024.06.010","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting young children and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal-controlled human infection by analyzing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with data from a concurrent study in younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. However, older adults who were protected from colonization showed increased degranulation of cluster of differentiation 8+ T cells, both before and after pneumococcal challenge. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 973-989"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0