The Neonatal Development of Intraepithelial and Lamina Propria Lymphocytes in the Murine Small Intestine

During early neonatal life, important changes occur in the gut. The intestine is challenged by both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to pelleted food leading to changes in microbial contents. This period seems essential for a complete development of the mucosal immune system. We investigated the development of both intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3, TCRαβ, TCRγδ, CD4, CD8α, CD8β, CD5, CD18, CD54, and CD49d. Our data show a clear increase in the number of LPL just before weaning, while the number of IEL increased after day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular communication of lymphocytes, showed an expression peak at weaning. In conclusion, the mouse mucosal immune system develops during the first 3 weeks of neonatal life leading to the formation of a more mature immune system at weaning.

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Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets

Nutrients ◽

10.3390/nu12072115 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2115

Author(s):

Stéphanie Ferret-Bernard ◽

Laurence Le Normand ◽

Véronique Romé ◽

Cindy Le Bourgot ◽

Julie Seeboth ◽

...

Keyword(s):

Immune System ◽

Lamina Propria ◽

Inflammatory Responses ◽

Intestinal Barrier ◽

Mucosal Immune System ◽

Food Ingredient ◽

Intestinal Immune System ◽

Maternal Supplementation ◽

Antigen Presenting ◽

The Impact

The early life period is crucial for the maturation of the intestinal barrier, its immune system, and a life-long beneficial host–microbiota interaction. The study aims to assess the impact of a beneficial dietary (short-chain fructooligosaccharides, scFOS) supplementation vs. a detrimental dietary environment (such as mycotoxin deoxynivalenol, DON) on offspring intestinal immune system developmental profiles. Sows were given scFOS-supplemented or DON-contaminated diets during the last 4 weeks of gestation, whereas force-feeding piglets with DON was performed during the first week of offspring life. Intestinal antigen-presenting cell (APC) subset frequency was analyzed by flow cytometry in the Peyer’s patches and in lamina propria and the responsiveness of intestinal explants to toll-like receptor (TLR) ligands was performed using ELISA and qRT-PCR from post-natal day (PND) 10 until PND90. Perinatal exposure with scFOS did not affect the ontogenesis of APC. While it early induced inflammatory responses in piglets, scFOS further promoted the T regulatory response after TLR activation. Sow and piglet DON contamination decreased CD16+ MHCII+ APC at PND10 in lamina propria associated with IFNγ inflammation and impairment of Treg response. Our study demonstrated that maternal prebiotic supplementation and mycotoxin contamination can modulate the mucosal immune system responsiveness of offspring through different pathways.

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Striking phenotypic and functional differences in lamina propria lymphocytes from the large and small intestine of mice

Life Sciences ◽

10.1016/j.lfs.2004.08.042 ◽

2005 ◽

Vol 76 (24) ◽

pp. 2783-2803 ◽

Cited By ~ 32

Author(s):

Aldo Arturo Reséndiz-Albor ◽

Rita Esquivel ◽

Rubén López-Revilla ◽

Leticia Verdín ◽

Leticia Moreno-Fierros

Keyword(s):

Small Intestine ◽

Lamina Propria ◽

Functional Differences ◽

Lamina Propria Lymphocytes

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Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves

BMC Genomics ◽

10.1186/s12864-016-2957-y ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 24

Author(s):

Guanxiang Liang ◽

Nilusha Malmuthuge ◽

Hua Bao ◽

Paul Stothard ◽

Philip J. Griebel ◽

...

Keyword(s):

Small Intestine ◽

Immune System ◽

Transcriptome Analysis ◽

System Development ◽

Mucosal Immune System ◽

Temporal Differences ◽

Immune System Development ◽

Neonatal Calves

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Distal Mucosal Site Stimulation by Kefir and Duration of the Immune Response

European Journal of Inflammation ◽

10.1177/1721727x0500300203 ◽

2005 ◽

Vol 3 (2) ◽

pp. 63-73 ◽

Cited By ~ 11

Author(s):

C. G. Vinderola ◽

J. Duarte ◽

D. Thangavel ◽

G. Perdigon ◽

E. Farnworth ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Oral Administration ◽

Lamina Propria ◽

Intestinal Mucosa ◽

Phagocytic Activity ◽

Mucosal Immune System ◽

Pulmonary Macrophages ◽

Bronchial Tissue ◽

Site Stimulation

Kefir is a fermented milk (drink) produced by the action of lactic acid bacteria, yeasts and acetic acid bacteria. We recently reported a comparative study on the effect of kefir containing viable or non-viable bacteria by studying their modulatory activity on the intestinal immune response. A functional dose was established in a murine model and the pattern of regulatory and pro-inflammatory cytokines induced was also studied. The existence of a common mucosal immune system implies that the immune cells stimulated in one mucosal tissue can spread and relocate through various mucosal sites. The aim of this work was to determine the effect of an oral administration of kefir on the duration of the intestinal mucosa immune response and the modulatory activity in distal mucosal sites, specifically in the peritoneal and pulmonary macrophages and in the bronchial tissue. BALB/c mice were fed with kefir or pasteurized kefir at doses previously determined as functional for intestinal mucosa immunomodulation. Kefir feeding was stopped and the number of IgA, IgG, IL-4, IL-6, IL-10, IIFNγ and TNFα producing cells was determined in the lamina propria of small intestine immediately, and after 2 and 7 days of kefir withdrawal. IgA producing cells were also measured in the bronchial tissue of lungs immediately and 2 and 7 days after kefir withdrawal. Phagocytic activity of peritoneal and pulmonary macrophages was also determined. The oral administration of kefir or pasteurized kefir increased the number of IgA+ cells not only in the gut lamina propria, but also in the bronchial tissue, supporting the concept of local antibody secretion after remote-site stimulation in the intestinal tract. Both peritoneal and pulmonary macrophages were activated by kefir or pasteurized kefir feeding. Peritoneal macrophages were stimulated faster than pulmonary macrophages (for kefir). The enhanced phagocytic activity achieved by kefir or pasteurized kefir lasted longer for the peritoneal than for the pulmonary macrophages. Due to the increased bronchial IgA and phagocytic activity of pulmonary macrophages after kefir feeding observed in this study, the oral administration of kefir could act as a natural adjuvant for enhancing the specific immune response against respiratory pathogens. The parameters studied returned to control values within a week of cessation of kefir administration. This would suggest that there is a low risk of overstimulating the gut mucosal immune system during periodic consumption of kefir.

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Intravital observation of adhesion of lamina propria lymphocytes to microvessels of small intestine in mice

Gastroenterology ◽

10.1053/gast.2002.31899 ◽

2002 ◽

Vol 122 (3) ◽

pp. 734-744 ◽

Cited By ~ 33

Author(s):

Hitoshi Fujimori ◽

Soichiro Miura ◽

Seiichiro Koseki ◽

Ryota Hokari ◽

Shunsuke Komoto ◽

...

Keyword(s):

Small Intestine ◽

Lamina Propria ◽

Lamina Propria Lymphocytes

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Small intestine mucosal immune system response to high-fat-high-cholesterol dietary supplementation in male rats

Food and Agricultural Immunology ◽

10.1080/09540105.2014.914467 ◽

2014 ◽

Vol 26 (2) ◽

pp. 293-304 ◽

Cited By ~ 5

Author(s):

M.S. Khalifeh ◽

S.S. Awaisheh ◽

O.H. Alameri ◽

W.M. Hananeh

Keyword(s):

Small Intestine ◽

Immune System ◽

Dietary Supplementation ◽

Mucosal Immune System ◽

Male Rats ◽

System Response ◽

High Cholesterol ◽

High Fat ◽

Immune System Response

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Interactions between gut-associated lymphoid tissue and colonization levels of indigenous, segmented, filamentous bacteria in the small intestine of mice

Canadian Journal of Microbiology ◽

10.1139/w98-122 ◽

1998 ◽

Vol 44 (12) ◽

pp. 1177-1182 ◽

Cited By ~ 26

Author(s):

J Snel ◽

C C Hermsen ◽

H J Smits ◽

N A Bos ◽

WMC Eling ◽

...

Keyword(s):

Small Intestine ◽

Immune System ◽

Lymphoid Tissue ◽

Immune Reaction ◽

Mucosal Immune System ◽

Filamentous Bacteria ◽

Segmented Filamentous Bacteria ◽

Swiss Mice ◽

Age Dependent ◽

Old Mice

Unlike most other indigenous bacteria, segmented filamentous bacteria (SFB) are potent activators of the mucosal immune system. SFB are strongly anchored to the epithelial cells of the small intestine where they have a preference for mucosal lymphoid epithelium. Since SFB are only present in high numbers shortly after weaning, it was investigated whether an SFB-induced immune reaction results in the removal of these bacteria from the small intestine. A correlation was found between age and colonization levels in the small intestines of SFB monoassociated Swiss mice. Five-week-old athymic BALB/c (nu/nu) mice showed lower colonization levels than their heterozygous littermates, but the opposite was found at the age of 12 weeks. However, SFB inoculation of germfree Swiss mice resulted in higher colonization levels in 5-week-old mice when compared with 4-month-old mice. We conclude that SFB colonization levels in the small intestine are likely influenced by the activity of the mucosal immune system. However, an additional age-dependent factor that modulates SFB colonization levels cannot be excluded.Key words: segmented filamentous bacteria, small intestine, gut-associated lymphoid tissue.

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Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid

Journal of Experimental Medicine ◽

10.1084/jem.20070602 ◽

2007 ◽

Vol 204 (8) ◽

pp. 1775-1785 ◽

Cited By ~ 1305

Author(s):

Cheng-Ming Sun ◽

Jason A. Hall ◽

Rebecca B. Blank ◽

Nicolas Bouladoux ◽

Mohamed Oukka ◽

...

Keyword(s):

Dendritic Cells ◽

Small Intestine ◽

Retinoic Acid ◽

Immune System ◽

Lamina Propria ◽

De Novo ◽

Lymphoid Organ ◽

Oral Exposure ◽

Intestinal Immune System ◽

Cell Conversion

To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3+ T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4+ T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ–derived DCs. This enhanced conversion by LpDCs was dependent on TGF-β and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.

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