The allergen-unchallenged enteric lesions in late allergic asthma are largely unknown. To clarify this point, BALB/c mice were sensitized by ovalbumin (OVA)/aluminum adjuvant intraperitoneally two times (on days 0 and 10) and then challenged with OVA intranasally on day 14 (asthma group). Four days after the challenge, small intestinal lesions were examined. ...

Deciphering the mechanisms of hematopoietic stem/progenitor cell (HSPC) mobilization and homing is important for the development of strategies to enhance the efficacy of HSPC transplantation and achieve the full potential of HSPC-based cellular therapy. Investigation of these mechanisms has revealed interdependence among the various molecules, pathways and cellular components involved, ...

PURPOSE OF REVIEW: Blood cell production is maintained by hematopoietic stem cells (HSCs) that reside in specialized niches within bone marrow. Treatment with granulocyte-colony stimulating factor (G-CSF) causes HSC egress from bone marrow niches and trafficking to the peripheral blood, a process termed 'mobilization'. Although the mobilization phenomenon has been ...

The potential to develop into any tissue makes pluripotent stem cells (PSCs) one of the most promising sources for cellular therapeutics. However, numerous hurdles exist to their clinical applications, three of the most concerning include the inability to separate therapeutic population from heterogeneously differentiated cultures, the risk of teratoma formation ...

Bone marrow (BM) derived mesenchymal stem cells (MSC) differentiate into cells of the mesodermal lineage but also, under certain experimental circumstances, into cells of the neuronal and glial lineage. Their therapeutic translation has been significantly boosted by the demonstration that MSC display significant also anti-proliferative, anti-inflammatory and anti-apoptotic features. These ...

Rhesus monkeys play a central role in model studies on human infectious diseases, and often mucosal organs are affected by these pathogens, e.g. HIV. However, a comparative investigation into lymphocyte composition from different mucosal tissues is still missing. Lymphocyte composition of duodenum, jejunum, ileum, colon, vagina, cervix, uterus and bronchoalveolar ...

Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle ...

This review analyzes and interprets the normal, pathogenic, and pathophysiological roles of stress and stress enzymes in mammalian development. Emerging data suggest that stem cells from early embryos are induced by stress to perform stress-enzyme-mediated responses that use the strategies of compensatory, prioritized, and reversible differentiation. These strategies have been ...

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow-derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ...

Mechanical signals of both low and high intensity are inhibitory to fat and anabolic to bone in vivo, and have been shown to directly affect mesenchymal stem cell pools from which fat and bone precursors emerge. To identify an idealized mechanical regimen which can regulate MSC fate, low intensity vibration ...

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin's lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin's lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have ...

The spatial orientation of the enteroendocrine cells along the crypt-villus axis is closely associated with their differentiation in the intestine. Here we studied this relationship using primary duodenal crypts and an ex vivo organoid system established from cholecystokinin-green fluorescent protein (CCK-GFP) transgenic mice. In the primary duodenal crypts, GFP+ cells ...

Under normal conditions, the great majority of hematopoietic stem/progenitors cells (HSPCs) reside in the bone marrow. The number of HSPCs in the circulation can be markedly increased in response to a number of stimuli, including hematopoietic growth factors, myeloablative agents and environmental stresses such as infection. The ability to 'mobilize' ...

Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8α(+) T cell ...

Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense against the intestinal bacteria. Although previous studies have demonstrated a protective role of IELs in the development of colitis, the data supporting a regulatory role for IELs are limited. The objective of this study was to examine the suppressive activity ...

Intestinal stem cells (ISCs) in the adult Drosophila midgut proliferate to self-renew and to produce differentiating daughter cells that replace those lost as part of normal gut function. Intestinal stress induces the activation of Upd/Jak/Stat signalling, which promotes intestinal regeneration by inducing rapid stem cell proliferation. We have investigated the ...

Interactions between lymphocytes and intestinal epithelial cells occur in the subepithelial space of the gastrointestinal tract. Normal human lamina propria lymphocytes (LPLs) induce differentiation of intestinal epithelial cells. The absence of LPLs in mice, such as in RAG1(-/-) mice, results in defects in epithelial cell differentiation. We investigated the role ...

Regulatory T cells (TR cells) play a crucial role in the regulation of intestinal inflammation. To examine the pathogenetic relevance of TR cells in inflammatory bowel disease (IBD), we evaluated their frequency in peripheral blood and inflamed and noninflamed mucosae of pediatric patients with IBD and age-matched controls without IBD; ...

Innate immune recognition of the bacterial cell wall constituent peptidoglycan by the cytosolic nucleotide-binding oligomerization domain 2 (Nod2) receptor has a pivotal role in the maintenance of intestinal mucosal homeostasis. Whereas peptidoglycan cleavage by gut-derived lysozyme preserves the recognition motif, the N-acetylmuramoyl-L-alanine amidase activity of the peptidoglycan recognition protein 2 ...

CD166 (also called activated leukocyte cell adhesion molecule [ALCAM]) is a marker of colorectal cancer (CRC) stem cells; it is expressed by aggressive tumors. Although the presence of CD166 at the tumor cell surface has been correlated with shortened survival, little is known about its function and expression in normal ...

Inflammatory bowel disease (IBD) can arise from genetic mutations that compromise intestinal epithelial cell integrity or immune regulation. SHIP has previously been shown to play a pivotal role in limiting the number of immunoregulatory cells and their function. To determine whether SHIP plays a pivotal role in control of immune ...

Generating lineage-committed intestinal stem cells from embryonic stem cells (ESCs) could provide a tractable experimental system for understanding intestinal differentiation pathways and may ultimately provide cells for regenerating damaged intestinal tissue. We tested a two-step differentiation procedure in which ESCs were first cultured with activin A to favor formation of ...

The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is ...

Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal ...

Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5(hi) stem cells persist life-long, yet crypts drift toward clonality ...

Self-renewal in the intestinal epithelia is fueled by a population of undifferentiated intestinal stem cells (ISCs) that give rise to daughter or progenitor cells, which can subsequently differentiate into the mature cell types required for normal gut function. The cellular signals that regulate self-renewal are poorly understood and the factors ...

During intestinal transplant (ITx) operation, intestinal lymphatics are not reconstituted. Consequently, trafficking immune cells drain freely into the abdominal cavity. Our aim was to evaluate whether leucocytes migrating from a transplanted intestine could be recovered from the abdominal draining fluid collected by a peritoneal drainage system in the early post-ITx ...

Unlike the ∼1% of γδ TCR-positive T cells being regularly present in blood and secondary lymphoid organs (peripheral γδ T cells), ∼50-60% of small intestinal intraepithelial lymphocytes (iIELs) in the mouse express the γδ TCR (γδ iIELs). In this study, we investigated the overlap and exchange of γδ iIELs and ...

Th17 cells constitute a subset of activated CD4(+) T cells, characterized by their production of interleukin (IL)-17, IL-17F, and IL-22, that play a critical role in host defence against extracellular pathogens. An intriguing feature of these cells is their selective and constitutive presence in the intestinal lamina propria. The development ...

Alemtuzumab has been used as an induction agent in organ transplantation over 10 years, but the effect of alemtuzumab on lymphocytes in small intestine was not clear. We investigate lymphocyte depletion and repopulation phenomena both in peripheral blood and small intestine of cynomolgus monkeys, to assess the model using in ...

Lymphocytic colitis (LC) is a disease of unknown aetiology. Among other pathogenetic possibilities, an abnormal reaction to a luminal antigen has been discussed. To clarify this fact, we characterized the inflammatory infiltrate in LC and compared it with the Th1 response-related coeliac disease (CD). Biopsies from 10 LC and 10 ...

Intestinal CD8αα intraepithelial T lymphocytes (T-IELs) have a key role in mucosal immunity and, unlike other T cells, were proposed to differentiate locally. In apparent contradiction, these cells were also shown to originate from a wave of thymus migrants colonizing the gut in the first 3 weeks after birth. We ...

Homeostasis in the Drosophila midgut is maintained by stem cells [1, 2]. The intestinal epithelium contains two types of differentiated cells that are lost and replenished: enteroendocrine (EE) cells and enterocytes (ECs). Intestinal stem cells (ISCs) are the only cells in the adult midgut that proliferate [3, 4], and ISC ...

The homeostatic renewal of the intestinal epithelium depends on regulation of proliferation and differentiation of stem/progenitor cells residing in a specific site, called the 'stem cell niche.' Thus, the reconstitution of the microenvironment of the stem cell niche may allow us to maintain intestinal stem/progenitor cells in culture for a ...

BACKGROUND: We previously demonstrated that in inflammatory bowel disease (IBD) there is enhanced production of interleukin (IL)-21, a cytokine that activates multiple pathways that sustain mucosal inflammation. However, the phenotype of IL-21-producing cells in IBD, and the cytokine(s) they coproduce, is not known. We here characterized the cell source of ...

Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and ...

Elucidating the mechanisms determining multipotent progenitor cell fate remains a fundamental project of contemporary biology. Various tissues of mice and men with defects in the zinc-finger transcriptional repressor Gfi1 have dramatic perturbations in the proportions of their differentiated cell types. In Gfi1-deficient intestinal epithelium there is a shift from mucous ...

Qiwei Baizhu Powder (QWBZP) is a traditional herbal prescription that has been used traditionally for the treatment of infantile diarrhea, including the infantile diarrhea caused by Human Rotavirus (HRV). In this study, we investigated the pharmacological activity of QWBZP extract. NIH suckling mice with HRV induced diarrhea were used. Density ...

The identification and separation of small intestinal epithelial stem cells are still on the preliminary stage. In this study, we planned to utilize immunohistochemistry, fluorescence-activated cell sorting (FACS) and RT-PCR to investigate the possibility of CD133 and CD44 as markers of human small intestinal epithelial stem cells. The expressions of ...

Alemtuzumab has been recently introduced for induction therapy in organ transplantation. However, the pathogenesis and molecular mechanism of the impact of such induction therapy on bacterial infections remain to be clarified. We found the alterations of Paneth cells including abnormal Paneth cell granules and expression of lysozyme and defensin 5 ...

Colonization of the gut by commensal bacteria modulates the induction of oral tolerance and allergy. However, how these intestinal bacteria modulate antigen-specific T cell responses induced by oral antigens remains unclear. In order to investigate this, we used germ-free (GF) ovalbumin (OVA)-specific T cell receptor transgenic (OVA23-3) mice. Conventional (CV) ...

BACKGROUND & AIMS: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). METHODS: ...

Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine the regulatory role proposed for CD30(+) T cells in this Th1-driven disease and the ...

MHC-related protein 1 (MR1) is a highly conserved MHC class I-like molecule. Human and murine mucosal associated invariant T (MAIT) cells are restricted by MR1 and express an invariant T cell receptor. Even though MR1 protein expression on the cell surface has not been demonstrated in vivo or ex vivo, ...

The ability of the host to respond to intestinal injury requires the regeneration of native tissue through a highly orchestrated response from the intestinal stem cells, a population of cells located within the intestinal crypts that have the capability to repopulate the entire villous. The field of intestinal stem cell ...

The immunosurveillance theory argues that the immune system recognizes tumour-specific antigens expressed by transformed cells, which results in the destruction of cancer precursors before they become clinically manifest. As a model for the development of cancer, we set out to study premalignant lesions and immune responses in sentinel lymph nodes ...

A 25-year-old Appaloosa gelding was evaluated for chronic weight loss and diarrhea. A clinical diagnosis of protein loosing enteropathy was made and the gelding was euthanized. Histology revealed neoplastic lymphocytes infiltrating the mucosa of the small and large intestine. Immunohistochemistry was positive for CD3, consistent with epitheliotropic T-cell lymphoma.

The cancer stem cell theory states that cancers contain tumor-forming cells that have the ability to self-renew as well as give rise to cells that differentiate. Cancer stem cells have been identified in several solid tumors, but stem cells in normal human esophagus or in Barrett's esophagus or adenocarcinoma have ...

The role of lactic acid bacteria in gut mucosal immunity was investigated by comparing the enhanced effects in the Peyer's patches and spleen of BALB/c mice fed daily with Lactobacillus paracasei subsp. paracasei NTU 101 for 3 to 9 weeks. After feeding with Lactobacillus, the percentage of CD4+ T cells ...

Intracellular protozoans of the genus Cryptosporidium are a major cause of diarrheal illness worldwide, especially in immunocompromised individuals. CD4(+) T cells and interferon-gamma are key factors in the control of cryptosporidiosis in human and murine models. Previous studies led us to hypothesize that CD8(+) T cells contribute to clearance of ...