Interleukin-2 activity of colonic lamina propria mononuclear cells in a rat model of experimental colitis

Using anin vitroautologous human system, the immunomodulatory function of colonic intraepithelial lymphocytes (IEL) on cytokine production by lamina propria mononuclear cells (LPMNC) has been investigated. In contrast to LPMNC, colonic IEL produced only low amounts of IL-10, interferon-γ and interleukin-2. However, co-culture experiments (IEL + LPMNC) have shown that IEL can enhance the PHA-induced synthesis of IL-2 and interferon-γ, but not IL-10 by LPMNC. Using a transwell filter culture system apparatus, this effect was shown not to require a cell-to-cell interaction. Thus, IELin vitromay modulate the cytokine synthesis of LPMNC, through the production of soluble factors. This may prove highly relevant in thein vivoimmune activation of the gastrointestinal mucosa.

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Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models

Microbiome ◽

10.1186/s40168-020-00991-x ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Francesco Strati ◽

Meritxell Pujolassos ◽

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Georgia Lattanzi ◽

...

Keyword(s):

Gut Microbiota ◽

Lamina Propria ◽

Mononuclear Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Ex Vivo ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Inkt Cells ◽

Lamina Propria Mononuclear Cells

Abstract Background The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Results Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Conclusions Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites.

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Lamina Propria Mononuclear Cells Express and Respond to Interleukin-2 Differently in Crohn's Disease and Ulcerative Colitis.

Internal Medicine ◽

10.2169/internalmedicine.35.679 ◽

1996 ◽

Vol 35 (9) ◽

pp. 679-685 ◽

Cited By ~ 7

Author(s):

Masataka SHINODA ◽

Jun-ichi HARUTA ◽

Mitsune TANIMOTO ◽

Takafumi ANDO ◽

Takehiko HOSOKAWA ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Lamina Propria ◽

Mononuclear Cells ◽

Interleukin 2 ◽

Lamina Propria Mononuclear Cells

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Products of enteropathogenic E. coli inhibit lymphokine production by gastrointestinal lymphocytes

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.271.5.g841 ◽

1996 ◽

Vol 271 (5) ◽

pp. G841-G848 ◽

Cited By ~ 10

Author(s):

J. M. Klapproth ◽

M. S. Donnenberg ◽

J. M. Abraham ◽

S. P. James

Keyword(s):

Mrna Expression ◽

Mononuclear Cells ◽

Interleukin 2 ◽

Enteric Bacteria ◽

Peripheral Blood Mononuclear ◽

Ifn Gamma ◽

E Coli ◽

Cd25 Expression ◽

Lamina Propria Mononuclear Cells ◽

Lymphokine Production

Previously we have shown that lysates of enteropathogenic Escherichia coli (EPEC) inhibit lymphokine production by mitogen-activated peripheral blood mononuclear cells (PBMCs). The aim of the present study was to determine whether products of EPEC alter lymphokine expression by gastrointestinal mucosal lymphocytes. Lysates from EPEC clones inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, IL-5, and interferon-gamma (IFN-gamma) but not IL-8 mRNA expression by lamina propria mononuclear cells isolated from surgically resected colon specimens. Inhibitory lysates did not significantly change CD25 expression on either CD4, CD8, or CD45R0 lymphocytes by flow cytometry. Bacterial supernatants of EPEC inhibited IL-2 and IL-5 protein secretion by mitogen-stimulated PBMCs. EPEC lysates inhibited IL-2 mRNA expression induced by lysates of nonpathogenic E. coli. In conclusion, EPEC contains a novel gene(s) that encodes factors that selectively inhibit IL-2, IL-4, IL-5, and IFN-gamma expression by mucosal mononuclear cells without affecting CD25 or IL-8 expression. Thus enteric bacteria can produce factors that may regulate the function of the gastrointestinal mucosal immune system.

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Activation of human lamina propria mononuclear cells in inflammatory bowel disease

Advances in Mucosal Immunology ◽

10.1007/978-94-009-1848-1_209 ◽

1990 ◽

pp. 675-680 ◽

Cited By ~ 2

Author(s):

S Scheiber ◽

G S Nash ◽

S Schloemann ◽

M Bertovich ◽

J Gamero ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Lamina Propria ◽

Bowel Disease ◽

Mononuclear Cells ◽

Lamina Propria Mononuclear Cells ◽

Inflammatory Bowel

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Generation of FOXP3+ Inducible Regulatory T Cells by Lamina Propria Mononuclear Cells in Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(11)62043-x ◽

2011 ◽

Vol 140 (5) ◽

pp. S-494

Author(s):

Christopher J. Moran ◽

Scott B. Snapper

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Regulatory T Cells ◽

Lamina Propria ◽

Bowel Disease ◽

Mononuclear Cells ◽

Lamina Propria Mononuclear Cells ◽

Inflammatory Bowel

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Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis in Mice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz193 ◽

2019 ◽

Vol 14 (6) ◽

pp. 856-866 ◽

Cited By ~ 4

Author(s):

Yasuki Higashimura ◽

Tomohisa Takagi ◽

Yuji Naito ◽

Kazuhiko Uchiyama ◽

Katsura Mizushima ◽

...

Keyword(s):

Bone Marrow ◽

Lamina Propria ◽

Zinc Deficiency ◽

Mononuclear Cells ◽

Interferon Regulatory Factor ◽

Nuclear Accumulation ◽

Regulatory Factor ◽

Colonic Inflammation ◽

Interferon Regulatory Factor 5 ◽

Lamina Propria Mononuclear Cells

Abstract Background and Aims Patients with inflammatory bowel disease [IBD], especially Crohn’s disease, often develop zinc deficiency. However, the precise mechanisms by which zinc deficiency affects IBD pathology, particularly intestinal macrophage function, remain unclear. We studied the effects of zinc deficiency on the development and progression of colitis in mice. Methods To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1−/− mice were then given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received a zinc chelator (TPEN; N,N,N′,N′-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were subsequently compared. Colonic lamina propria mononuclear cells were isolated by enzymatic digestion and were examined using flow cytometry. To generate mouse bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with mouse macrophage-colony stimulating factor. Results Zinc deficiency aggravates colonic inflammation through the activation of type 17 helper T [Th17] cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina propria mononuclear cells obtained from inflamed colon. Interferon-γ plus lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which is strongly related to Th17 development. Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is closely involved in IL-23p19 induction in zinc-deficient macrophages. Conclusions Zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis. This activation is controlled by subcellular distribution of interferon-regulatory factor 5.

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