Abstract:
:Proper colonic injury response requires myeloid-derived cells and Toll-like receptor/Myd88 signaling. However, the precise role of Myd88 signaling specifically in myeloid-derived cells that occurs during tissue damage is unclear. Therefore, we created a mouse line with Myd88 expression restricted to myeloid lineages (Myd88(-/-); LysM(Cre/+); ROSA26(Myd88/+); herein Mlcr). In these mice, Myd88 was appropriately expressed and mediated responses to bacterial ligand exposure in targeted cells. Importantly, the severe colonic epithelial phenotype observed in dextran sodium sulfate-injured Myd88(-/-) mice was rescued by the genetic modification of Mlcr mice. During injury, myeloid cell activation and enrichment of Ptsg2-expressing stromal cells occurred within the mesenchyme that surrounded the crypt bases of Mlcr and Myd88(+/-) mice but not Myd88(-/-) mice. Interestingly, these cellular changes to the crypt base mesenchyme also occurred, but to a lesser extent in uninjured Mlcr mice. These results show that Myd88 expression in myeloid cells was sufficient to rescue intestinal injury responses, and surprisingly, these cells appear to require an additional Myd88-dependent signal from a non-myeloid cell type during homeostasis.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Malvin NP,Seno H,Stappenbeck TSdoi
10.1038/mi.2011.65subject
Has Abstractpub_date
2012-03-01 00:00:00pages
194-206issue
2eissn
1933-0219issn
1935-3456journal_volume
5pub_type
杂志文章abstract::The development of the primitive gut in the multicellular aquatic eukaryote was driven by the insufficient absorption of nutrients from the oceanic soup. The anatomy of this evolving specialized system invited its colonization by environmental prokaryotes and resulted in the establishment of the intestinal microflora....
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.123
更新日期:2010-01-01 00:00:00
abstract::Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.41
更新日期:2017-01-01 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::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::The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to ill...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2007.5
更新日期:2008-01-01 00:00:00
abstract::Mesenteric lymph nodes (MLNs), that drain the large and small intestine, are critical sites for the induction of oral tolerance. Although depletion of CD4 T cells in the intestinal lamina propria is a hallmark of HIV infection, CD4 T cell dynamics in MLNs is less known due to the lack of accessibility to these LNs. We...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0174-0
更新日期:2019-07-01 00:00:00
abstract::The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung. Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection. This cytokine is strongl...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0206-9
更新日期:2020-01-01 00:00:00
abstract::Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mou...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-018-0033-4
更新日期:2018-09-01 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::Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epi...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2017.107
更新日期:2018-03-01 00:00:00
abstract::T helper (Th)1 and Th2 cells play decisive roles in the regulation of resistance vs. susceptibility to pulmonary cryptococcosis. To study the function of interleukin (IL)-4 receptor (IL-4R) on Th cells in pulmonary cryptococcosis, we infected mice specifically lacking IL-4Rα on CD4(+) T cells (Lck(Cre)IL-4Rα(-/lox) mi...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.9
更新日期:2012-05-01 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::Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell exp...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2017.86
更新日期:2018-05-01 00:00:00
abstract::Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptide...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0188-7
更新日期:2019-09-01 00:00:00
abstract::Alpha B-crystallin (CRYAB) is an important member of the small heat shock protein family, and plays a protective and therapeutic role in neurological inflammation. CRYAB expression was assessed in cultured HT29 and Caco-2 cells and inflamed mucosa of patients with inflammatory bowel disease (IBD) and colitis models in...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0198-5
更新日期:2019-11-01 00:00:00
abstract::Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as t...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.14
更新日期:2012-05-01 00:00:00
abstract::The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.142
更新日期:2016-09-01 00:00:00
abstract::Insufficient T-cell responses contribute to the increased burden of viral respiratory disease in infancy. Neonatal dendritic cells (DCs) often provide defective activation of pathogen-specific T cells through mechanisms that are incompletely understood, which hinders vaccine design for this vulnerable age group. Enhan...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0234-5
更新日期:2020-03-01 00:00:00
abstract::The roles of macrophages in type 2-driven inflammation and fibrosis remain unclear. Here, using CD11b-diphtheria toxin receptor (DTR) transgenic mice and three models of interleukin 13 (IL-13)-dependent inflammation, fibrosis, and immunity, we show that CD11b(+) F4/80(+) Ly6C(+) macrophages are required for the mainte...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.34
更新日期:2016-01-01 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::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 generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cell...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0218-5
更新日期:2020-01-01 00:00:00
abstract::Molecular mechanisms regulating transforming growth factor-beta (TGF-beta) induction of Foxp3 (forkhead box P3) expression and thus induction of induced regulatory T cells (Tregs) have been the focus of a great deal of study in recent years. It has become clear that this process is influenced by a number of factors as...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2010.7
更新日期:2010-05-01 00:00:00
abstract::Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin-13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat-containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13-treated esophageal epitheli...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.98
更新日期:2016-05-01 00:00:00
abstract::Our studies have focused on understanding the mechanisms of interactions between the indigenous intestinal flora and the mammalian host in both physiological and nonphysiological conditions. In particular, we have focused on the function of innate microbial pattern recognition by Toll-like receptors in the context of ...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2008.49
更新日期:2008-11-01 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::Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2011.16
更新日期:2011-09-01 00:00:00
abstract::Nucleotide oligomerization domain (NOD)2 is a member of the NOD-like receptor family of proteins that initiate inflammatory responses when exposed to ligands derived from bacterial components that gain access to the intracellular milieu. It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2008.42
更新日期:2008-11-01 00:00:00
abstract::Leukotriene B4 receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0175-z
更新日期:2019-09-01 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