Mucosal Immunology最新文献

{"title":"Dysregulated NOX1-NOS2 activity as hallmark of ileitis in mice","authors":"Julie Drieu La Rochelle ,&nbsp;Josie Ward ,&nbsp;Emily Stenke ,&nbsp;Yuting Yin ,&nbsp;Misaki Matsumoto ,&nbsp;Richard Jennings ,&nbsp;Gabriella Aviello ,&nbsp;Ulla G. Knaus","doi":"10.1016/j.mucimm.2024.08.012","DOIUrl":"10.1016/j.mucimm.2024.08.012","url":null,"abstract":"<div><div>Inflammation of the ileum, or ileitis, is commonly caused by Crohn’s disease (CD) but can also accompany ulcerative colitis (backwash ileitis), infections or drug-related damage. Oxidative tissue injury triggered by reactive oxygen species (ROS) is considered part of the ileitis etiology. However, not only elevated ROS but also permanently decreased ROS are associated with inflammatory bowel disease (IBD). While very early onset IBD (VEO-IBD) is associated with a spectrum of <em>NOX1</em> variants, how NOX1 inactivation contributes to disease development remains ill-defined. Besides propagating signaling responses, NOX1 provides superoxide for peroxynitrite formation in the epithelial barrier. Here we report that NOX4, an H₂O₂-generating NADPH oxidase with documented tissue protective effects in the intestine and other tissues, limits the generation of ileal peroxynitrite by NOX1/NOS2. Deletion of NOX4 leads to persistent peroxynitrite excess, hyperpermeability, villus blunting, muscular hypertrophy, chemokine/cytokine upregulation and dysbiosis. Conversely, SAMP1/YitFc mice, a CD-like ileitis model, showed age-dependent NOX1/NOS2 downregulation preventing ileal peroxynitrite formation in homeostasis and LPS-induced acute inflammation. Deficiency in NOX1 correlated with the upregulation of antimicrobial peptides, suggesting that ileal peroxynitrite acts as chemical barrier and microbiota modifier in the ileum.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1326-1336"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154590","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}

{"title":"Exposure to bacterial PAMPs before RSV infection exacerbates innate inflammation and disease via IL-1α and TNF-α","authors":"Amber R. Owen ,&nbsp;Ana Farias ,&nbsp;Anne-Marie Levins ,&nbsp;Ziyin Wang ,&nbsp;Sophie L. Higham ,&nbsp;Matthias Mack ,&nbsp;John S. Tregoning ,&nbsp;Cecilia Johansson","doi":"10.1016/j.mucimm.2024.08.002","DOIUrl":"10.1016/j.mucimm.2024.08.002","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections. Understanding why some individuals get more serious disease may help with diagnosis and treatment. One possible risk factor underlying severe disease is bacterial exposure before RSV infection. Bacterial exposure has been associated with increased respiratory viral-induced disease severity but the mechanism remains unknown. Respiratory bacterial infections or exposure to their pathogen associated molecular patterns (PAMPs) trigger innate immune inflammation, characterised by neutrophil and inflammatory monocyte recruitment and the production of inflammatory cytokines. We hypothesise that these changes to the lung environment alter the immune response and disease severity during subsequent RSV infection. To test this, we intranasally exposed mice to LPS, LTA or <em>Acinetobacter baumannii</em> (an airway bacterial pathogen) before RSV infection and observed an early induction of disease, measured by weight loss, at days 1–3 after infection. Neutrophils or inflammatory monocytes were not responsible for driving this exacerbated weight loss. Instead, exacerbated disease was associated with increased IL-1α and TNF-α, which orchestrated the recruitment of innate immune cells into the lung. This study shows that exposure to bacterial PAMPs prior to RSV infection increases the expression of IL-1α and TNF-α, which dysregulate the immune response resulting in exacerbated disease.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1184-1198"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913316","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}

{"title":"Conserved B cell signaling, activation, and differentiation in porcine jejunal and ileal Peyer’s patches despite distinct immune landscapes","authors":"Jayne E. Wiarda ,&nbsp;Adrienne L. Shircliff ,&nbsp;Sage R. Becker ,&nbsp;Judith B. Stasko ,&nbsp;Sathesh K. Sivasankaran ,&nbsp;Mark R. Ackermann ,&nbsp;Crystal L. Loving","doi":"10.1016/j.mucimm.2024.08.005","DOIUrl":"10.1016/j.mucimm.2024.08.005","url":null,"abstract":"<div><div>Peyer’s patches (PPs) are B cell-rich sites of intestinal immune induction, yet PP-associated B cell signaling, activation, and differentiation are poorly defined. Single-cell and spatial transcriptomics were completed to study B cells from porcine jejunum and ileum containing PPs. Intestinal locations had distinct immune landscapes, including more follicular B cells in ileum and increased MHC-II-encoding gene expression in jejunal B cells. Despite distinct landscapes, conserved B cell dynamics were detected across intestinal locations, including B cell signaling to <em>CD4⁺</em> macrophages that are putative phagocytic, cytotoxic, effector cells and deduced routes of B cell activation/differentiation, including resting B cells migrating into follicles to replicate/divide or differentiate into antibody-secreting cells residing in intestinal crypts. A six-biomarker panel recapitulated transcriptomics findings of B cell phenotypes, frequencies, and spatial locations via <em>ex vivo</em> and <em>in situ</em> staining. Findings convey conserved B cell dynamics across intestinal locations containing PPs, despite location-specific immune environments. Results establish a benchmark of B cell dynamics for understanding intestinal immune induction important to promoting gut/overall health.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1222-1241"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988354","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}

{"title":"CSF1R inhibition by PLX5622 reduces pulmonary fungal infection by depleting MHCIIhi interstitial lung macrophages","authors":"Sally H. Mohamed ,&nbsp;Eliane Vanhoffelen ,&nbsp;Man Shun Fu ,&nbsp;Pui Hei Lau ,&nbsp;Sofia Hain ,&nbsp;Laura Seldeslachts ,&nbsp;Emilie Cosway ,&nbsp;Graham Anderson ,&nbsp;Laura McCulloch ,&nbsp;Greetje Vande Velde ,&nbsp;Rebecca A. Drummond","doi":"10.1016/j.mucimm.2024.08.007","DOIUrl":"10.1016/j.mucimm.2024.08.007","url":null,"abstract":"<div><div>PLX5622 is a small molecular inhibitor of the CSF1 receptor (CSF1R) and is widely used to deplete macrophages within the central nervous system (CNS). We investigated the impact of PLX5622 treatment in wild-type C57BL/6 mice and discovered that one-week treatment with PLX5622 was sufficient to deplete interstitial macrophages in the lung and brain-infiltrating Ly6C^low patrolling monocytes, in addition to CNS-resident macrophages. These cell types were previously indicated to act as infection reservoirs for the pathogenic fungus <em>Cryptococcus neoformans</em>. We found that PLX5622-treated mice had significantly reduced fungal lung infection and reduced extrapulmonary dissemination to the CNS but not to the spleen or liver. Fungal lung infection mapped to MHCII^hi interstitial lung macrophages, which underwent significant expansion during infection following monocyte replenishment and not local division. Although PLX5622 depleted CNS infiltrating patrolling monocytes, these cells did not accumulate in the fungal-infected CNS following pulmonary infection. In addition, Nr4a1-deficient mice, which lack patrolling monocytes, had similar control and dissemination of <em>C. neoformans</em> infection to wild-type controls. PLX5622 did not directly affect CD4 T-cell responses, or significantly affect production of antibody in the lung during infection. However, we found that mice lacking lymphocytes had reduced numbers of MHCII^hi interstitial macrophages in the lung, which correlated with reduced infection load. Accordingly, PLX5622 treatment did not alter fungal burdens in the lungs of lymphocyte-deficient mice. Our data demonstrate that PLX5622 may help reduce lung burden of pathogenic fungi that utilise CSF1R-dependent myeloid cells as infection reservoirs, an effect which is dependent on the presence of lymphocytes.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1256-1272"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018080","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}

{"title":"Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis","authors":"Yulan Ye ,&nbsp;Changqin Liu ,&nbsp;Ruijin Wu ,&nbsp;Dengfeng Kang ,&nbsp;Han Gao ,&nbsp;Huiying Lv ,&nbsp;Zhongsheng Feng ,&nbsp;Yanhong Shi ,&nbsp;Zhanju Liu ,&nbsp;Liang Chen","doi":"10.1016/j.mucimm.2024.07.010","DOIUrl":"10.1016/j.mucimm.2024.07.010","url":null,"abstract":"<div><div>Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4⁺ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4⁺ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4⁺ T cells of UC patients compared with that in Crohn’s disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn’s Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn’s disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4⁺ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&amp;Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4⁺ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4⁺ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4⁺ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1161-1173"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889716","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}

{"title":"Itaconate suppresses house dust mite-induced allergic airways disease and Th2 cell differentiation","authors":"Yiran Li ,&nbsp;Shilpi Singh ,&nbsp;Haley A. Breckenridge ,&nbsp;Tracy X. Cui ,&nbsp;Thomas M. Vigil ,&nbsp;Jordan E. Kreger ,&nbsp;Jing Lei ,&nbsp;Harrison K.A. Wong ,&nbsp;Peter Sajjakulnukit ,&nbsp;Xiaofeng Zhou ,&nbsp;J. Kelley Bentley ,&nbsp;Costas A. Lyssiotis ,&nbsp;Richard M. Mortensen ,&nbsp;Marc B. Hershenson","doi":"10.1016/j.mucimm.2024.08.001","DOIUrl":"10.1016/j.mucimm.2024.08.001","url":null,"abstract":"<div><div>Itaconate was initially identified as an antimicrobial compound produced by myeloid cells. Beyond its antimicrobial role, itaconate may also serve as a crucial metabolic and immune modulator. We therefore examined the roles of aconitate decarboxylase 1 (Acod1) and itaconate in house dust mite (HDM)-sensitized and −challenged mice, a model of T helper 2 (Th2)-driven allergic airways disease. HDM treatment induced lung <em>Acod1</em> mRNA expression and bronchoalveolar lavage (BAL) itaconate levels in wild-type C57BL/6 mice. Acod1 knockout mice (Acod1-KO) with negligible BAL itaconate showed heightened HDM-induced type 2 cytokine expression, increased serum IgE, and enhanced recruitment of Th2 cells in the lung, indicating a shift towards a more pronounced Th2 immune response. Acod1-KO mice also showed increased eosinophilic airway inflammation and hyperresponsiveness. Experiments in chimeric mice demonstrated that bone marrow from Acod1-KO mice is sufficient to increase type 2 cytokine expression in wild-type mice, and that restitution of bone marrow from wild type mice attenuates mRNA expression of Th2 cytokines in Acod1-KO mice. Specific deletion of Acod1 in lysozyme-secreting macrophages (<em>LysM</em>-cre⁺<em>Acod1</em>^flox/flox) recapitulated the exaggerated phenotype observed in whole-body Acod1-KO mice. Adoptive transfer of Acod1-KO bone marrow-derived macrophages also increased lung mRNA expression of Th2 cytokines. In addition, treatment of Th2-polarized CD4 cells with itaconate impeded Th2 cell differentiation, as shown by reduced expression of Gata3 and decreased release of IL-5 and IL-13. Finally, public datasets of human samples show lower <em>Acod1</em> expression in subjects with allergic asthma, consistent with a protective role of itaconate in asthma pathogenesis. Together, these data suggest that itaconate plays a protective, immunomodulatory role in limiting airway type 2 inflammation after allergen challenge by attenuating T cell responses.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1174-1183"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988355","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}

{"title":"Microbiota-derived butyrate inhibits cDC development via HDAC inhibition, diminishing their ability to prime T cells","authors":"Anna Andrusaite ,&nbsp;Jennifer Lewis ,&nbsp;Annika Frede ,&nbsp;Andrew Farthing ,&nbsp;Verena Kästele ,&nbsp;Jennifer Montgomery ,&nbsp;Allan Mowat ,&nbsp;Elizabeth Mann ,&nbsp;Simon Milling","doi":"10.1016/j.mucimm.2024.08.003","DOIUrl":"10.1016/j.mucimm.2024.08.003","url":null,"abstract":"<div><div>Conventional dendritic cells (cDC) are central to maintaining the balance between protective immune responses and tolerance to harmless antigens, especially in the intestine. Short chain fatty acids (SCFAs) such as butyrate play critical roles in regulating intestinal immunity, but the underlying mechanisms remain unclear. Here we demonstrate that microbiota-derived butyrate alters intestinal cDC populations <em>in vivo</em> resulting in decreased numbers of the cDC2 lineage. By establishing a novel <em>in vitro</em> culture model, we show that butyrate has a direct and selective ability to repress the development of cDC2 from cDC precursors, an effect that is independent of G-protein coupled receptors (GPCRs) and is due to inhibition of histone deacetylase 3. Finally, cDC derived from pre-cDC in the presence of butyrate <em>in vitro</em> express lower levels of costimulatory molecules and have a decreased ability to prime naïve T cells. Together, our data show that butyrate affects the developmental trajectory of cDC, selectively repressing the cDC2 lineage and reducing their ability to stimulate T cells. These properties may help explain the ability of butyrate to maintain homeostasis in the intestine.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1199-1211"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982795","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}

{"title":"Controlling functional homeostasis of ileal resident macrophages by vitamin B12 during steady state and Salmonella infection in mice","authors":"Yong Ge ,&nbsp;Mojgan Zadeh ,&nbsp;Cheshta Sharma ,&nbsp;Yang-Ding Lin ,&nbsp;Alexey A. Soshnev ,&nbsp;Mansour Mohamadzadeh","doi":"10.1016/j.mucimm.2024.08.011","DOIUrl":"10.1016/j.mucimm.2024.08.011","url":null,"abstract":"<div><div>Dietary micronutrients, particularly vitamin B12 (VB12), profoundly influence the physiological maintenance and function of intestinal cells. However, it is still unclear whether VB12 modulates the transcriptional and metabolic programming of ileal macrophages (iMacs), thereby contributing to intestinal homeostasis. Using multiomic approaches, we demonstrated that VB12 primarily supports the cell cycle activity and mitochondrial metabolism of iMacs, resulting in increased cell frequency compared to VB12 deficiency. VB12 also retained the ability to promote maintenance and metabolic regulation of iMacs during intestinal infection with <em>Salmonella</em> Typhimurium (STm). On the contrary, depletion of iMacs by inhibiting CSF1R signaling significantly increased host susceptibility to STm and prevented VB12-mediated pathogen reduction. These results thus suggest that regulation of VB12-dependent iMacs critically controls STm expansion, which may be of new relevance to advance our understanding of this vitamin and to strategically formulate sustainable therapeutic nutritional regimens that improve human gut health.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1314-1325"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142183290","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}

{"title":"RIPK3 and caspase-8 interpret cytokine signals to regulate ILC3 survival in the gut","authors":"Ann M. Joseph ,&nbsp;Anees Ahmed ,&nbsp;Jeremy Goc ,&nbsp;Veronika Horn ,&nbsp;Brooke Fiedler ,&nbsp;Dario Garone ,&nbsp;John B. Grigg ,&nbsp;Jazib Uddin ,&nbsp;Fei Teng ,&nbsp;Melanie Fritsch ,&nbsp;Eric Vivier ,&nbsp;Gregory F. Sonnenberg","doi":"10.1016/j.mucimm.2024.08.004","DOIUrl":"10.1016/j.mucimm.2024.08.004","url":null,"abstract":"<div><div>Group 3 innate lymphoid cells (ILC3s) are abundant in the developing or healthy intestine to critically support tissue homeostasis in response to microbial colonization. However, intestinal ILC3s are reduced during chronic infections, colorectal cancer, or inflammatory bowel disease (IBD), and the mechanisms driving these alterations remain poorly understood. Here we employed RNA sequencing of ILC3s from IBD patients and observed a significant upregulation of RIPK3, the central regulator of necroptosis, during intestinal inflammation. This was modeled in mice where we found that intestinal ILC3s express RIPK3, with conventional (c)ILC3s exhibiting high RIPK3 and low levels of pro-survival genes relative to lymphoid tissue inducer (LTi)-like ILC3s. ILC3-specific RIPK3 is promoted by gut microbiota, further upregulated following enteric infection, and dependent upon IL-23R and STAT3 signaling. However, lineage-specific deletion of RIPK3 revealed a redundant role in ILC3 survival, due to a blockade of RIPK3-mediated necroptosis by caspase 8, which was also activated in response to enteric infection. In contrast, lineage-specific deletion of caspase 8 resulted in loss of cILC3s from the healthy intestine and all ILC3 subsets during enteric infection, which increased pathogen burdens and gut inflammation. This function of caspase 8 required catalytic activity induced by TNF or TL1A and was dispensable if RIPK3 was simultaneously deleted. Caspase 8 activation and cell death were associated with increased Fas on ILC3s, and the Fas-FasL pathway was upregulated by cILC3s during enteric infection, which could restrain the abundance of intestinal ILC3s. Collectively, these data reveal that interpretation of key cytokine signals controls ILC3 survival following microbial challenge, and that an imbalance of these pathways, such as in IBD or across ILC3 subsets, provokes depletion of tissue-protective ILC3s from the inflamed intestine.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 6","pages":"Pages 1212-1221"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976179","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}

{"title":"Bite-sized immunology; damage and microbes educating immunity at the gingiva","authors":"Joanne E. Konkel,&nbsp;Joshua R. Cox,&nbsp;Kelly Wemyss","doi":"10.1016/j.mucimm.2024.07.004","DOIUrl":"10.1016/j.mucimm.2024.07.004","url":null,"abstract":"<div><div>Immune cells residing at the gingiva experience diverse and unique signals, tailoring their functions to enable them to appropriately respond to immunological challenges and maintain tissue integrity. The gingiva, defined as the mucosal barrier that surrounds and supports the teeth, is the only barrier site completely transected by a hard structure, the tooth. The tissue is damaged in early life during tooth eruption and chronically throughout life by the process of mastication. This occurs alongside challenges typical of barrier sites, including exposure to invading pathogens, the local commensal microbial community and environmental antigens. This review will focus on the immune network safeguarding gingival integrity, which is far less understood than that resident at other barrier sites. A detailed understanding of the gingiva-resident immune network is vital as it is the site of the inflammatory disease periodontitis, the most common chronic inflammatory condition in humans which has well-known detrimental systemic effects. Furthering our understanding of how the immune populations within the gingiva develop, are tailored in health, and how this is dysregulated in disease would further the development of effective therapies for periodontitis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 5","pages":"Pages 1141-1150"},"PeriodicalIF":7.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748610","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}