scholarly journals Chemokine Receptor CCR9 Contributes to the Localization of Plasma Cells to the Small Intestine

2004 ◽  
Vol 199 (3) ◽  
pp. 411-416 ◽  
Author(s):  
Oliver Pabst ◽  
Lars Ohl ◽  
Meike Wendland ◽  
Marc-André Wurbel ◽  
Elisabeth Kremmer ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lamina Propria ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Intestinal Epithelial ◽  
Cell Type Composition ◽  
Type Composition ◽  
Iga Response

Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

scholarly journals Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1522
Author(s):  
Bin Zeng ◽  
Hailong Wang ◽  
Junyi Luo ◽  
Meiying Xie ◽  
Zhengjiang Zhao ◽  
...  
Keyword(s):  
Small Intestine ◽  
Extracellular Vesicles ◽  
Immunoglobulin A ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Intestinal Immunity ◽  
In Vivo Experiments ◽  
Porcine Milk

Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.

Immune disorders of the gastrointestinal tract

2010 ◽  
pp. 2244-2256
Author(s):  
D.J. Unsworth
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
B Lymphocytes ◽  
Lamina Propria ◽  
Thoracic Duct ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Systemic Circulation ◽  
Lymphoid Follicles

The gastrointestinal tract is protected by gut-associated lymphoid tissue that provides an environment where interaction occurs between luminal antigen and specially adapted immune tissue in Peyer’s patches (small intestine only) or lymphoid follicles. T and B lymphocytes primed in the gut migrate into the systemic circulation via the thoracic duct but home preferentially to the lamina propria of the intestine. Plasma cells of the lamina propria secrete immunoglobulin A as a dimer linked by a joining peptide....

scholarly journals Immunoglobulin A Antibodies against Ricin A and B Subunits Protect Epithelial Cells from Ricin Intoxication

2006 ◽  
Vol 74 (6) ◽  
pp. 3455-3462 ◽  
Author(s):  
Nicholas J. Mantis ◽  
Carolyn R. McGuinness ◽  
Oluwakemi Sonuyi ◽  
Gary Edwards ◽  
Stephanie A. Farrant
Keyword(s):  
Epithelial Cells ◽  
Immunoglobulin A ◽  
Human Monocyte ◽  
Intestinal Epithelial ◽  
Mesenteric Lymph Nodes ◽  
Cell Monolayers ◽  
Iga Antibodies ◽  
Ricin A

ABSTRACT Epithelial cells of the respiratory and gastrointestinal tracts are extremely vulnerable to the cytotoxic effects of ricin, a Shiga-like toxin with ribosome-inactivating properties. While mucosal immunity to ricin correlates with secretory immunoglobulin A (IgA) antibody levels in vivo, the potential of IgA to protect epithelial cells from ricin in vitro has not been examined due to the unavailability of well-defined antitoxin IgA antibodies. Here we report the characterization of four monoclonal IgA antibodies (IgA MAbs) produced from the Peyer's patches and mesenteric lymph nodes of BALB/c mice immunized intragastrically with ricin toxoid. Two IgA MAbs (33G2 and 35H6) were active against ricin's lectin subunit (RTB), and two (23D7 and 25A4) reacted with the toxin's enzymatic subunit (RTA). All four IgA MAbs neutralized ricin in a Vero cell cytotoxicity assay, blocked toxin-induced interleukin-8 release by the human monocyte/macrophage cell line 28SC, and protected polarized epithelial cell monolayers from ricin-mediated protein synthesis inhibition. 33G2 and 35H6 reduced ricin binding to the luminal surfaces of human intestinal epithelial cells to undetectable levels in tissue section overlay assays, whereas 23D7 had no effect on toxin attachment. 23D7 and 25A4 did, however, reduce ricin transcytosis across MDCK II cell monolayers, possibly by interfering with intracellular toxin transport. We conclude that IgA antibodies against RTA and RTB can protect mucosal epithelial cells from ricin intoxication.

scholarly journals Generation of human chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases

2021 ◽  
Author(s):  
Beatrice Xuan Ho ◽  
Jeremy Pang ◽  
Qian Hua Phua ◽  
Lee Chuen Liew ◽  
Boon Min Poh ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Pluripotent Stem Cells ◽  
In Vitro Model ◽  
Cell Type ◽  
In Vivo Models ◽  
Cell Type Composition ◽  
Type Composition ◽  
Vitro Model

Recent progress on murine and human cardiac organoids have provided understanding to the developmental processes of the heart. However, there is still an unfulfilled need for improved modelling of cardiovascular diseases using human cardiac organoids. Herein, we report successful generation of intrinsically formed human chambered cardiac organoids (CCO) and highlight its utility in modelling disease. Single cell transcriptomic profiling of CCOs showed appropriate cardiovascular cell type composition exhibiting improved maturation. Functionally, CCOs recapitulated clinical cardiac hypertrophy by exhibiting thickened chamber walls, reduced ejection fractions, increased myofibrillar disarray and tachycardia. Therefore, CCOs improve current capabilities of disease modelling as an in vitro model bridging the gap to in vivo models, with the ability to assess functional parameters that previously can only be achieved in animal systems.

scholarly journals Design of Polymeric Nanocapsules for Intranasal Vaccination against Mycobacterium Tuberculosis: Influence of the Polymeric Shell and Antigen Positioning

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 489
Author(s):  
Lara Diego-González ◽  
José Crecente-Campo ◽  
Matthew John Paul ◽  
Mahavir Singh ◽  
Rajko Reljic ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immunoglobulin A ◽  
In Vivo Experiments ◽  
Polymeric Nanocapsules ◽  
Infectious Microorganism ◽  
Iga Response ◽  
Efficacious Vaccine

Tuberculosis (TB) is the leading cause of death from a single infectious microorganism and Bacillus Calmette Guerin (BCG), the only authorized vaccine, does not confer protection against pulmonary TB. Based on the hypothesis that mucosal protection could help to prevent the infection at the site of entrance, the objective of this work was to develop an intranasal vaccine against Mycobacterium tuberculosis (Mtb), the microorganism that causes TB. Our approach consisted of the use of polymeric nanocapsules (NCs) with an oily core and a polymer shell made of chitosan (CS) or inulin/polyarginine (INU/pArg). The immunostimulant Imiquimod, a Toll-like receptor-7 (TLR-7) agonist, was encapsulated in the oily core and a fusion protein, formed by two antigens of Mtb, was absorbed either onto the NC surface (CS:Ag and INU:pArg:Ag) or between two polymer layers (INU:Ag:pArg) in order to assess the influence of the antigen positioning on the immune response. Although CS NCs were more immunostimulant than the INU/pArg NCs in vitro, the in vivo experiments showed that INU:pArg:Ag NCs were the only prototype inducing an adequate immunoglobulin A (IgA) response. Moreover, a previous immunization with BCG increased the immune response for CS NCs but, conversely, decreased for INU/pArg NCs. Further optimization of the antigen and the vaccination regime could provide an efficacious vaccine, using the INU:pArg:Ag NC prototype as nanocarrier.

scholarly journals Fibroblast growth factor 10 alters the balance between goblet and Paneth cells in the adult mouse small intestine

2015 ◽  
Vol 308 (8) ◽  
pp. G678-G690 ◽  
Author(s):  
Denise Al Alam ◽  
Soula Danopoulos ◽  
Kathy Schall ◽  
Frederic G. Sala ◽  
Dana Almohazey ◽  
...  
Keyword(s):  
Small Intestine ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Paneth Cells ◽  
Intestinal Epithelial ◽  
Mouse Small Intestine ◽  
Fibroblast Growth Factor 10 ◽  
Goblet Cell Differentiation

Intestinal epithelial cell renewal relies on the right balance of epithelial cell migration, proliferation, differentiation, and apoptosis. Intestinal epithelial cells consist of absorptive and secretory lineage. The latter is comprised of goblet, Paneth, and enteroendocrine cells. Fibroblast growth factor 10 (FGF10) plays a central role in epithelial cell proliferation, survival, and differentiation in several organs. The expression pattern of FGF10 and its receptors in both human and mouse intestine and their role in small intestine have yet to be investigated. First, we analyzed the expression of FGF10, FGFR1, and FGFR2, in the human ileum and throughout the adult mouse small intestine. We found that FGF10, FGFR1b, and FGFR2b are expressed in the human ileum as well as in the mouse small intestine. We then used transgenic mouse models to overexpress Fgf10 and a soluble form of Fgfr2b, to study the impact of gain or loss of Fgf signaling in the adult small intestine. We demonstrated that overexpression of Fgf10 in vivo and in vitro induces goblet cell differentiation while decreasing Paneth cells. Moreover, FGF10 decreases stem cell markers such as Lgr5, Lrig1, Hopx, Ascl2, and Sox9. FGF10 inhibited Hes1 expression in vitro, suggesting that FGF10 induces goblet cell differentiation likely through the inhibition of Notch signaling. Interestingly, Fgf10 overexpression for 3 days in vivo and in vitro increased the number of Mmp7/Muc2 double-positive cells, suggesting that goblet cells replace Paneth cells. Further studies are needed to determine the mechanism by which Fgf10 alters cell differentiation in the small intestine.

scholarly journals Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

Science ◽  
2019 ◽  
Vol 363 (6430) ◽  
pp. 993-998 ◽  
Author(s):  
Joep Grootjans ◽  
Niklas Krupka ◽  
Shuhei Hosomi ◽  
Juan D. Matute ◽  
Thomas Hanley ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Intestinal Epithelial ◽  
Healthy Humans ◽  
Mucosal Surfaces ◽  
Iga Response ◽  
Independent Expansion ◽  
Secretory Immunoglobulin

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell–dependent and –independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.

The protease phenotype and crystalline nature of the granules of intraepithelial mast cells in Trichinella spiralis-infected mice

1995 ◽  
Vol 53 ◽  
pp. 818-819
Author(s):  
D.S. Friend ◽  
N. Ghildyal ◽  
M.F. Gurish ◽  
K.F. Austen ◽  
R.L. Stevens
Keyword(s):  
Small Intestine ◽  
Mast Cells ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Trichinella Spiralis ◽  
Intestinal Epithelial ◽  
Carboxypeptidase A ◽  
C3h Mice ◽  
Granule Morphology ◽  
Crystalline Nature

Trichinella spiralis induces a profound mastocytosis and eosinophilia in the small intestine of the infected mouse. Mouse mast cells (MC) store in their granules various combinations of at least five chymotryptic chymases [designated mouse MC protease (mMCP) 1 to 5], two tryptic proteases designated mMCP-6 and mMCP-7 and an exopeptidase, carboxypeptidase A (mMC-CPA). Using antipeptide, protease -specific antibodies to these MC granule proteases, immunohistochemistry was done to determine the distribution, number and protease phenotype of the MCs in the small intestine and spleen 10 to >60 days after Trichinella infection of BALB/c and C3H mice. TEM was performed to evaluate the granule morphology of the MCs between intestinal epithelial cells and in the lamina propria (mucosal MCs) and in the submucosa, muscle and serosa of the intestine (submucosal MCs).As noted in the table below, the number of submucosal MCs remained constant throughout the study. In contrast, on day 14, the number of MCs in the mucosa increased ~25 fold. Increased numbers of MCs were observed between epithelial cells in the mucosal crypts, in the lamina propria and to a lesser extent, between epithelial cells of the intestinal villi.

scholarly journals Bioactive Compounds from Herbal Medicine Targeting Multiple Myeloma

2021 ◽  
Vol 11 (10) ◽  
pp. 4451
Author(s):  
Coralia Cotoraci ◽  
Alina Ciceu ◽  
Alciona Sasu ◽  
Eftimie Miutescu ◽  
Anca Hermenean
Keyword(s):  
Multiple Myeloma ◽  
Survival Rate ◽  
Plasma Cells ◽  
Inhibition Of Proliferation ◽  
In Vivo Experiments ◽  
Clonal Proliferation ◽  
Hematological Cancers ◽  
Monoclonal Proteins

Multiple myeloma (MM) is one of the most widespread hematological cancers. It is characterized by a clonal proliferation of malignant plasma cells in the bone marrow and by the overproduction of monoclonal proteins. In recent years, the survival rate of patients with multiple myeloma has increased significantly due to the use of transplanted stem cells and of the new therapeutic agents that have significantly increased the survival rate, but it still cannot be completely cured and therefore the development of new therapeutic products is needed. Moreover, many patients have various side effects and face the development of drug resistance to current therapies. The purpose of this review is to highlight the bioactive active compounds (flavonoids) and herbal extracts which target dysregulated signaling pathway in MM, assessed by in vitro and in vivo experiments or clinical studies, in order to explore their healing potential targeting multiple myeloma. Mechanistically, they demonstrated the ability to promote cell cycle blockage and apoptosis or autophagy in cancer cells, as well as inhibition of proliferation/migration/tumor progression, inhibition of angiogenesis in the tumor vascular network. Current research provides valuable new information about the ability of flavonoids to enhance the apoptotic effects of antineoplastic drugs, thus providing viable therapeutic options based on combining conventional and non-conventional therapies in MM therapeutic protocols.

scholarly journals Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Moe Ichikawa ◽  
Hiroki Akamine ◽  
Michika Murata ◽  
Sumito Ito ◽  
Kazuo Takayama ◽  
...  
Keyword(s):  
Small Intestine ◽  
Drug Absorption ◽  
Cell Model ◽  
Negative Effects ◽  
Piggybac Transposon ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Cyp3a4 Expression

AbstractCaco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.

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