scholarly journals The Intestinal Chemokine Thymus-expressed Chemokine (CCL25) Attracts IgA Antibody-secreting Cells

2002 ◽  
Vol 195 (2) ◽  
pp. 269-275 ◽  
Author(s):  
Edward P. Bowman ◽  
Nelly A. Kuklin ◽  
Kenneth R. Youngman ◽  
Nicole H. Lazarus ◽  
Eric J. Kunkel ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Immunoglobulin A ◽  
The Body ◽  
Intestinal Epithelial ◽  
Mucosal Surfaces ◽  
Intestinal Pathogen ◽  
Lymph Node Cells ◽  
Iga Antibody ◽  
Iga Production ◽  
Antibody Secreting Cells

Immunoglobulin A (IgA) provides protection against pathogens at mucosal surfaces. Chemotactic responses have been hypothesized to target IgA plasma cells involved in mucosal immune responses. We show here that thymus-expressed chemokine (TECK, CCL25) is a potent and selective chemoattractant for IgA antibody-secreting cells (ASC), efficiently recruiting IgA-producing cells from spleen, Peyer's patches, and mesenteric lymph node. Cells secreting IgA antibody in response to rotavirus, an intestinal pathogen, also respond well. In contrast, IgG– and IgM–ASC respond poorly. Epithelial cells in the small intestines, a principal site of IgA–ASC localization and IgA production in the body, highly and selectively express TECK. The migration of IgA–ASC to the intestinal epithelial cell chemokine TECK may help target IgA-producing cells to the gut wall, thus helping define and segregate the intestinal immune response.

scholarly journals Supplemental β-carotene increases IgA-secreting cells in mammary gland and IgA transfer from milk to neonatal mice

2010 ◽  
Vol 105 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Yoshitaka Nishiyama ◽  
Miki Sugimoto ◽  
Shuntaro Ikeda ◽  
Shinichi Kume
Keyword(s):  
Mammary Gland ◽  
Stomach Contents ◽  
Neonatal Mice ◽  
Mucosal Surfaces ◽  
Pregnancy And Lactation ◽  
Pregnant Mice ◽  
Iga Antibody ◽  
Iga Production ◽  
Β Carotene ◽  
Antibody Secreting Cells

Mortality of neonates continues to be a major problem in humans and animals. IgA provides protection against microbial antigens at mucosal surfaces. Although β-carotene supplementation has been expected to enhance retinoic acid-mediated immune response in neonates, the exact mechanism by which β-carotene enhances IgA production is still unclear. We investigated the effect of supplemental β-carotene for maternal mice during pregnancy and lactation on IgA antibody-secreting cells (ASC) in mammary gland and guts and on IgA transfer from milk to neonatal mice. Pregnant mice were fed untreated or 50 mg/kg β-carotene-supplemented diets from 6·5 d postcoitus (dpc) to 14 d postpartum (dpp). Supplemental β-carotene increased the numbers of IgA ASC in mammary gland (P < 0·05) and ileum (P < 0·001), and also mRNA expression of IgA C-region in ileum (P < 0·05) of maternal mice at 14 dpp, but few IgA ASC were detected in mammary gland at 17·5 dpc. IgA concentration in stomach contents, which represents milk IgA level, was significantly higher (P < 0·01) in neonatal mice born to β-carotene-supplemented mothers at 7 and 14 dpp, and IgA concentration in serum, stomach contents and faeces increased (P < 0·001) drastically with age. These results suggest that β-carotene supplementation for maternal mice during pregnancy and lactation is useful for enhancing IgA transfer from maternal milk to neonates owing to the increase in IgA ASC in mammary gland and ileum during lactation.

scholarly journals Effects of supplemental β-carotene on mucosal IgA induction in the jejunum and ileum of mice after weaning

2013 ◽  
Vol 111 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Keita Nishida ◽  
Miki Sugimoto ◽  
Shuntaro Ikeda ◽  
Shinichi Kume
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Retinoid X Receptor ◽  
Mucosal Surfaces ◽  
Iga Antibody ◽  
Iga Production ◽  
Β Carotene ◽  
Antibody Secreting Cells

An adequate immune system is required to prevent diarrhoea in neonates, and IgA provides protection against microbial antigens on mucosal surfaces. Although β-carotene supplementation has been expected to enhance the retinoic acid (RA)-mediated immune response in neonates, the exact mechanism of the enhancement of mucosal IgA production in the small intestine by β-carotene is still unclear. In the present study, we investigated the effect of supplemental β-carotene on the concentrations of IgA, the numbers of IgA antibody-secreting cells (ASC) and the mRNA expressions of IgA C-region, CCL25, retinoid X receptor (RXR) α, retinoic acid receptor (RAR) α and RARγ in the jejunum and ileum of weanling mice. Weanling mice were fed rodent feed or 50 mg/kg β-carotene-supplemented rodent feed for 7, 14 or 21 d. The concentrations of IgA and the numbers of IgA ASC in the jejunum and ileum of mice increased markedly with age, and supplemental β-carotene increased the concentrations of IgA, the numbers of IgA ASC and the mRNA expressions of IgA C-region, CCL25 and RARγ in the jejunum after 14 and 21 d of treatment. Supplemental β-carotene increased the numbers of IgA ASC in the ileum after 14 and 21 d of treatment, but the concentrations of IgA in the ileum were not affected by β-carotene supplementation. The mRNA expressions of RXRα and RARα in the jejunum and those of RXRα and RARγ in the ileum after 21 d of treatment were enhanced by β-carotene supplementation. These results indicate that β-carotene supplementation in weanling mice is effective to enhance mucosal IgA induction in the jejunum or ileum and that the effects are mainly due to the RA-mediated immune response.

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.

scholarly journals Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage

2000 ◽  
Vol 68 (7) ◽  
pp. 3830-3839 ◽  
Author(s):  
Dörthe Externest ◽  
Barbara Meckelein ◽  
M. Alexander Schmidt ◽  
Andreas Frey
Keyword(s):  
Cholera Toxin ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Secretory Iga ◽  
Enzyme Linked Immunosorbent Assay ◽  
Routine Diagnostics ◽  
Significant Relationships ◽  
Serum Igg ◽  
Mucosal Surfaces ◽  
Secretory Immunoglobulin

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.

scholarly journals Segmented Filamentous Bacteria Are Potent Stimuli of a Physiologically Normal State of the Murine Gut Mucosal Immune System

1999 ◽  
Vol 67 (4) ◽  
pp. 1992-2000 ◽  
Author(s):  
Gwen L. Talham ◽  
Han-Qing Jiang ◽  
Nicolaas A. Bos ◽  
John J. Cebra
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immunoglobulin A ◽  
Mucosal Immune System ◽  
Filamentous Bacteria ◽  
Mesenteric Lymph Nodes ◽  
Segmented Filamentous Bacteria ◽  
Iga Antibody ◽  
Autochthonous Bacteria ◽  
Iga Production

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer’s patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4+ T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal,Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4+, CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.

scholarly journals Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia

2017 ◽  
Vol 114 (3) ◽  
pp. 568-573 ◽  
Author(s):  
Jay R. Thiagarajah ◽  
Jeffrey Chang ◽  
Jeremy A. Goettel ◽  
Alan S. Verkman ◽  
Wayne I. Lencer
Keyword(s):  
Hydrogen Peroxide ◽  
Epithelial Cells ◽  
Focal Adhesions ◽  
The Body ◽  
Colonic Epithelium ◽  
Colonic Epithelial Cells ◽  
Signaling Mechanism ◽  
Aquaporin 3 ◽  
Mucosal Surfaces ◽  
Intestinal Pathogen

The colonic epithelium provides an essential barrier against the environment that is critical for protecting the body and controlling inflammation. In response to injury or gut microbes, colonic epithelial cells produce extracellular hydrogen peroxide (H2O2), which acts as a potent signaling molecule affecting barrier function and host defense. In humans, impaired regulation of H2O2 in the intestine has been associated with early-onset inflammatory bowel disease and colon cancer. Here, we show that signal transduction by H2O2 depends on entry into the cell by transit through aquaporin-3 (AQP3), a plasma membrane H2O2-conducting channel. In response to injury, AQP3-depleted colonic epithelial cells showed defective lamellipodia, focal adhesions, and repair after wounding, along with impaired H2O2 responses after exposure to the intestinal pathogen Citrobacter rodentium. Correspondingly, AQP3−/− mice showed impaired healing of superficial wounds in the colon and impaired mucosal innate immune responses against C. rodentium infection, manifested by reduced crypt hyperplasia, reduced epithelial expression of IL-6 and TNF-α, and impaired bacterial clearance. These results elucidate the signaling mechanism of extracellular H2O2 in the colonic epithelium and implicate AQP3 in innate immunity at mucosal surfaces.

scholarly journals Predominance of Serotype-Specific Mucosal Antibody Response in Shigella flexneri-Infected Humans Living in an Area of Endemicity

2001 ◽  
Vol 69 (9) ◽  
pp. 5230-5234 ◽  
Author(s):  
Voahangy Rasolofo-Razanamparany ◽  
Anne-Marie Cassel-Beraud ◽  
Jean Roux ◽  
Philippe J. Sansonetti ◽  
Armelle Phalipon
Keyword(s):  
Antibody Response ◽  
Natural Infection ◽  
Shigella Flexneri ◽  
Immunoglobulin A ◽  
Cross Reactivity ◽  
Bacterial Antigen ◽  
Humoral Immune ◽  
Mucosal Antibody ◽  
Iga Antibody ◽  
Antibody Secreting Cells

ABSTRACT The mucosal humoral immune response elicited followingShigella flexneri infection in patients living in Antananarivo districts (Madagascar Island) was evaluated by measuring the gut-derived, circulating immunoglobulin A (IgA) antibody-secreting cells (ASC) specific for the major bacterial antigen lipopolysaccharide (LPS). Fifty, 34, 11, and 5% of the S. flexneri-positive patients were infected with serotypes 2a, 1a, 4a, and 3a, respectively. The total number of IgA ASC in infected patients increased significantly, compared to the number in healthy controls, early after the onset of disease. The number of anti-homologous LPS IgA ASC varied among individuals and peaked between days 5 and 10 after the onset of the disease. In the S. flexneri 1a- and 2a-infected patients, the level of IgA ASC cross-reactivity to heterologous S. flexneri serotypes was weak. These data indicate that S. flexneri 2a and 1a are the predominant strains responsible for shigellosis in this area of endemicity and that the anti-LPS antibody response following natural infection is mainly directed against serotype-specific determinants.

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 Maturation and Trafficking Markers on Rotavirus-Specific B Cells during Acute Infection and Convalescence in Children

2004 ◽  
Vol 78 (20) ◽  
pp. 10967-10976 ◽  
Author(s):  
María C. Jaimes ◽  
Olga L. Rojas ◽  
Eric J. Kunkel ◽  
Nicole H. Lazarus ◽  
Dulce Soler ◽  
...  
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Fluorescent Protein ◽  
Acute Infection ◽  
Intestinal Infection ◽  
Cell Homing ◽  
Specific Memory ◽  
Iga Antibody ◽  
Green Fluorescent ◽  
Antibody Secreting Cells

ABSTRACT We have previously studied B cells, from people and mice, that express rotavirus-specific surface immunoglobulin (RV-sIg) by flow cytometry with recombinant virus-like particles that contain green fluorescent protein. In the present study we characterized circulating B cells with RV-sIg in children with acute and convalescent infection. During acute infection, circulating RV-sIgD− B cells are predominantly large, CD38high, CD27high, CD138+/−, CCR6−, α4β7+, CCR9+, CCR10+, cutaneous lymphocyte antigen-negative (CLA−), L-selectinint/−, and sIgM+, sIgG−, sIgA+/− lymphocytes. This phenotype likely corresponds to gut-targeted plasma cells and plasmablasts. During convalescence the phenotype switches to small and large lymphocytes, CD38int/−, CD27int/−, CCR6+, α4β7+/−, CCR9+/− and CCR10−, most likely representing RV-specific memory B cells with both gut and systemic trafficking profiles. Of note, during acute RV infection both total and RV-specific murine IgM and IgA antibody-secreting cells migrate efficiently to CCL28 (the CCR10 ligand) and to a lesser extent to CCL25 (the CCR9 ligand). Our results show that CCR10 and CCR9 can be expressed on IgM as well as IgA antibody-secreting cells in response to acute intestinal infection, likely helping target these cells to the gut. However, these intestinal infection-induced plasmablasts lack the CLA homing receptor for skin, consistent with mechanisms of differential CCR10 participation in skin T versus intestinal plasma cell homing. Interestingly, RV memory cells generally lack CCR9 and CCR10 and instead express CCR6, which may enable recruitment to diverse epithelial sites of inflammation.

scholarly journals B cell residency but not T cell–independent IgA switching in the gut requires innate lymphoid cells

2021 ◽  
Vol 118 (27) ◽  
pp. e2106754118
Author(s):  
Mingzhu Zheng ◽  
Kairui Mao ◽  
Difeng Fang ◽  
Dan Li ◽  
Jun Lyu ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Lymphoid Structures ◽  
Iga Production ◽  
Cell Adoptive Transfer

Immunoglobulin A (IgA)–producing plasma cells derived from conventional B cells in the gut play an important role in maintaining the homeostasis of gut flora. Both T cell–dependent and T cell–independent IgA class switching occurs in the lymphoid structures in the gut, whose formation depends on lymphoid tissue inducers (LTis), a subset of innate lymphoid cells (ILCs). However, our knowledge on the functions of non-LTi helper-like ILCs, the innate counter parts of CD4 T helper cells, in promoting IgA production is still limited. By cell adoptive transfer and utilizing a unique mouse strain, we demonstrated that the generation of IgA-producing plasma cells from B cells in the gut occurred efficiently in the absence of both T cells and helper-like ILCs and without engaging TGF-β signaling. Nevertheless, B cell recruitment and/or retention in the gut required functional NKp46−CCR6+ LTis. Therefore, while CCR6+ LTis contribute to the accumulation of B cells in the gut through inducing lymphoid structure formation, helper-like ILCs are not essential for the T cell–independent generation of IgA-producing plasma cells.

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