Abstract:
:Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process. In vivo depletion of macrophages caused reduced differentiation of splenic IFN-γ- and IL-10-producing Tr1-like cells after CT-TG2-gliadin but not gliadin peptide feed. Splenic macrophages, rather than dendritic cells, constitutively expressed increased mRNA levels of the endopeptidase Cathepsin D; macrophage depletion significantly reduced splenic Cathepsin D expression in vivo and Cathepsin D efficiently degraded recombinant γ-gliadin in vitro. In response to CT-TG2-gliadin uptake, macrophages enhanced the expression of Il27p28, a cytokine that favored differentiation of gliadin-specific Tr1-like cells in vitro, and was previously reported to increase Cathepsin D activity. Conversely, IL-27 neutralization in vivo inhibited splenic IFN-γ- and IL-10-secreting Tr1-like-cell differentiation after CT-TG2-gliadin feed. Our data infer that endopeptidase mediated gliadin degradation by macrophages and concomitant IL-27 production drive differentiation of splenic gliadin-specific Tr1-like cells.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
van Leeuwen MA,Costes LMM,van Berkel LA,Simons-Oosterhuis Y,du Pré MF,Kozijn AE,Raatgeep HC,Lindenbergh-Kortleve DJ,van Rooijen N,Koning F,Samsom JNdoi
10.1038/mi.2016.76subject
Has Abstractpub_date
2017-05-01 00:00:00pages
635-649issue
3eissn
1933-0219issn
1935-3456pii
mi201676journal_volume
10pub_type
杂志文章abstract::Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respecti...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2014.114
更新日期:2015-01-01 00:00:00
abstract::Eosinophils are granulocytes, typically implicated as end-stage effector cells in type-II immune responses. They are capable of producing a wide array of pre-formed molecules which render them with vast potential to influence a wide variety of processes. Nonetheless, eosinophil research has traditionally focused on th...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/s41385-020-0281-y
更新日期:2020-07-01 00:00:00
abstract::Acute intestinal inflammation includes the early accumulation of neutrophils (PMN). Based on recent evidence that PMN infiltration "imprints" changes in the local tissue environment through local oxygen depletion and the release of adenine nucleotides, we hypothesized that the interaction between transmigrating PMN an...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0237-2
更新日期:2020-03-01 00:00:00
abstract::The mammalian gut microbiota is essential for normal intestinal development, renewal, and repair. Injury to the intestinal mucosa can occur with infection, surgical trauma, and in idiopathic inflammatory bowel disease. Repair of mucosal injury, termed restitution, as well as restoration of intestinal homeostasis invol...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.84
更新日期:2014-05-01 00:00:00
abstract::Viral respiratory tract infections (RTI) pose a high burden on the youngest members of our society. Several risk factors are known for severe viral respiratory disease. However, a large proportion of the severe RTI cannot be explained by these risk factors. A growing body of evidence shows that the composition of the ...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2013.93
更新日期:2014-03-01 00:00:00
abstract::How the immune system senses aeroallergens and triggers an aberrant inflammation is poorly understood. Dectin-2 is a house dust mite (HDM)-sensing pattern recognition receptor. In a 3-week mouse model of repeated intranasal HDM challenge, anti-Dectin-2 potently attenuated the characteristic allergic inflammation and a...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.74
更新日期:2014-05-01 00:00:00
abstract::Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.80
更新日期:2017-05-01 00:00:00
abstract::Celiac disease (CD) is a chronic small intestinal inflammation precipitated by gluten ingestion. According to case reports, interferon (IFN)-α administration may induce development of overt CD. Plasmacytoid dendritic cells (PDCs) were thought to be the source of IFN-α and promote a T helper type 1 response leading to ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.136
更新日期:2013-09-01 00:00:00
abstract::Mucus, with its burden of inspired particulates and pathogens, is cleared from mucosal surfaces of the airways by cilia beating within the periciliary layer (PCL). The PCL is held to be "watery" and free of mucus by thixotropic-like forces arising from beating cilia. With radii of gyration ~250 nm, however, polymeric ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.81
更新日期:2013-03-01 00:00:00
abstract::Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2014.105
更新日期:2015-07-01 00:00:00
abstract::Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation,...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.116
更新日期:2014-07-01 00:00:00
abstract::Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2-/- mice were...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-018-0106-4
更新日期:2019-03-01 00:00:00
abstract::The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although lit...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2010.54
更新日期:2010-11-01 00:00:00
abstract::Microbial metabolites are an emerging class of mediators influencing CD4+ T-cell function. To advance the understanding of direct causal microbial factors contributing to Crohn's disease, we screened 139 predicted Crohn's disease-associated microbial metabolites for their bioactivity on human CD4+ T-cell functions ind...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-018-0022-7
更新日期:2019-03-01 00:00:00
abstract::The communities of bacteria that reside in the intestinal tract are in constant competition within this dynamic and densely colonized environment. At homeostasis, the equilibrium that exists between these species and strains is shaped by their metabolism and also by pathways of active antagonism, which drive competiti...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/s41385-018-0053-0
更新日期:2019-01-01 00:00:00
abstract::Helicobacter suis infects the stomachs of both animals and humans, and can induce gastric mucosa-associated lymphoid tissue (MALT) lymphomas. It is known that CXC chemokine ligand 13 (CXCL13) is highly expressed in the Helicobacter-infected mice and gastric MALT lymphoma patients, but the pathway that links the activa...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2014.14
更新日期:2014-09-01 00:00:00
abstract::Vaccine-mediated prevention of primary infection with human immunodeficiency virus (HIV) may require the sustained production of antibody at mucosal portals of entry. Here, we describe a novel approach of repeated mucosal immunization by delivering an HIV-1 envelope glycoprotein (gp) in a gel formulated for intravagin...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.110
更新日期:2010-01-01 00:00:00
abstract::The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activa...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.128
更新日期:2016-09-01 00:00:00
abstract::The interleukin-23 (IL-23) pathway has emerged as a promising therapeutic target for inflammatory bowel disease. Although the pathogenic role of IL-23 receptor (IL-23R) on T lymphocytes is well established, its function on innate immune cells has not been thoroughly examined. Here we investigate the consequence of IL-...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2011.54
更新日期:2012-01-01 00:00:00
abstract::Celiac disease is a multifactorial disorder and provides a privileged model to decipher how the interplay between environmental and genetic factors can alter mucosal tolerance to a food antigen, lead to chronic intestinal inflammation, and ultimately promote T-cell lymphomagenesis. Here we summarize how HLA-DQ2/8 mole...
journal_title:Mucosal immunology
pub_type: 评论,杂志文章,评审
doi:10.1038/mi.2008.75
更新日期:2009-01-01 00:00:00
abstract::There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13Rα2 was necessary for IBD in mice deficient in the anti-in...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0189-6
更新日期:2019-09-01 00:00:00
abstract::The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct fr...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.67
更新日期:2014-05-01 00:00:00
abstract::Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involv...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2008.15
更新日期:2008-07-01 00:00:00
abstract::Association mapping and candidate gene studies within inflammatory bowel diseases (IBD) linkage regions, as well as genome-wide association studies in Crohn's disease (CD) have led to the discovery of multiple risk genes, but these explain only a fraction of the genetic susceptibility observed in IBD. We have thus bee...
journal_title:Mucosal immunology
pub_type: 杂志文章,多中心研究
doi:10.1038/mi.2007.15
更新日期:2008-03-01 00:00:00
abstract::Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral ...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2010.25
更新日期:2010-07-01 00:00:00
abstract::Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4(+) T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that H...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.11
更新日期:2013-11-01 00:00:00
abstract::Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2017.1
更新日期:2017-11-01 00:00:00
abstract::Human papillomaviruses (HPV)-related cervical cancer is the second leading cause of cancer death in women worldwide. Despite active development, HPV E6/E7 oncogene-specific therapeutic vaccines have had limited clinical efficacy to date. Here, we report that intravaginal (IVAG) instillation of CpG-ODN (TLR9 agonist) o...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.83
更新日期:2013-03-01 00:00:00
abstract::Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.127
更新日期:2010-03-01 00:00:00
abstract::The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samp...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.129
更新日期:2010-03-01 00:00:00